knockout mice

Summary

Summary: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

Top Publications

  1. ncbi Interleukin-10 and the interleukin-10 receptor
    K W Moore
    Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology Inc, Palo Alto, California 94304, USA
    Annu Rev Immunol 19:683-765. 2001
  2. ncbi Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis
    Seth Rakoff-Nahoum
    Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell 118:229-41. 2004
  3. ncbi Toll-like receptor signalling
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and ERATO, Japan Science and Technology Agency, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nat Rev Immunol 4:499-511. 2004
  4. ncbi Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product
    K Hoshino
    Department of Biochemistry, Hyogo College of Medicine, Japan
    J Immunol 162:3749-52. 1999
  5. pmc Disseminated tuberculosis in interferon gamma gene-disrupted mice
    A M Cooper
    Department of Microbiology, Colorado State University, Fort Collins 80523
    J Exp Med 178:2243-7. 1993
  6. ncbi The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells
    Ivaylo I Ivanov
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Cell 126:1121-33. 2006
  7. pmc Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance
    Justin I Odegaard
    Division of Endocrinology, Metabolism and Gerontology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305 5103, USA
    Nature 447:1116-20. 2007
  8. ncbi XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor
    H Yoshida
    Graduate School of Biostudies, Kyoto University, Kyoto 606 8304, Japan
    Cell 107:881-91. 2001
  9. pmc An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection
    J L Flynn
    Howard Hughes Medical Institute, Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461
    J Exp Med 178:2249-54. 1993
  10. pmc Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity
    Yueh Ming Loo
    Department of Immunology, University of Washington School of Medicine, Box 357650, Seattle, WA 98195 7650, USA
    J Virol 82:335-45. 2008

Research Grants

  1. Discovery metabolite profiling of the prolyl peptidases
    Alan Saghatelian; Fiscal Year: 2009
  2. Cardiac Physiology and Imaging Core for Mouse in Vivo
    Kirk Peterson; Fiscal Year: 2009
  3. Understanding the Cognitive Impact of Early Life Epilepsy
    Frances Jensen; Fiscal Year: 2009
  4. Biomedical Simulations Resource (BMSR)
    DAVID Z D apos ARGENIO; Fiscal Year: 2010
  5. Biomedical Simulations Resource (BMSR)
    DAVID D ARGENIO; Fiscal Year: 2009
  6. Duke Comp Cancer Inst. Core Support Grant
    HERBERT KIM LYERLY; Fiscal Year: 2010
  7. Molecular Biology Core Laboratory
    David Russell; Fiscal Year: 2009
  8. MOLECULAR & CELLULAR MECHANISMS IN TRANSFUSION MEDICINE
    Peter J Newman; Fiscal Year: 2011
  9. Gamma-Synuclein-Mediated Regulation of Norepinephrine Transporter
    Anita Sidhu; Fiscal Year: 2009
  10. Gamma-Synuclein-Mediated Regulation of Norepinephrine Transporter
    Anita Sidhu; Fiscal Year: 2010

Detail Information

Publications306 found, 100 shown here

  1. ncbi Interleukin-10 and the interleukin-10 receptor
    K W Moore
    Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology Inc, Palo Alto, California 94304, USA
    Annu Rev Immunol 19:683-765. 2001
    ..This review highlights findings that have advanced our understanding of IL-10 and its receptor, as well as its in vivo function in health and disease...
  2. ncbi Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis
    Seth Rakoff-Nahoum
    Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell 118:229-41. 2004
    ..These findings reveal a novel function of TLRs-control of intestinal epithelial homeostasis and protection from injury-and provide a new perspective on the evolution of host-microbial interactions...
  3. ncbi Toll-like receptor signalling
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and ERATO, Japan Science and Technology Agency, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nat Rev Immunol 4:499-511. 2004
  4. ncbi Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product
    K Hoshino
    Department of Biochemistry, Hyogo College of Medicine, Japan
    J Immunol 162:3749-52. 1999
    ..Overexpression of wild-type TLR4 but not the mutant TLR4 from C3H/HeJ mice activated NF-kappaB. Taken together, the present study demonstrates that TLR4 is the gene product that regulates LPS response...
  5. pmc Disseminated tuberculosis in interferon gamma gene-disrupted mice
    A M Cooper
    Department of Microbiology, Colorado State University, Fort Collins 80523
    J Exp Med 178:2243-7. 1993
    ..These data, therefore, indicate that although IFN-gamma may not be needed for DTH expression, it plays a pivotal and essential role in protective cellular immunity to tuberculosis infection...
  6. ncbi The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells
    Ivaylo I Ivanov
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Cell 126:1121-33. 2006
    ..Together, these studies suggest that RORgammat is a key regulator of immune homeostasis and highlight its potential as a therapeutic target in inflammatory diseases...
  7. pmc Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance
    Justin I Odegaard
    Division of Endocrinology, Metabolism and Gerontology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305 5103, USA
    Nature 447:1116-20. 2007
    ....
  8. ncbi XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor
    H Yoshida
    Graduate School of Biostudies, Kyoto University, Kyoto 606 8304, Japan
    Cell 107:881-91. 2001
    ..Our results reveal features of the UPR conserved during evolution and clarify the relationship between IRE1- and ATF6-dependent pathways...
  9. pmc An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection
    J L Flynn
    Howard Hughes Medical Institute, Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461
    J Exp Med 178:2249-54. 1993
    ..In contrast to control mice, gko mice exhibit heightened tissue necrosis and succumb to a rapid and fatal course of tuberculosis that could be delayed, but not prevented, by treatment with exogenous recombinant IFN-gamma...
  10. pmc Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity
    Yueh Ming Loo
    Department of Immunology, University of Washington School of Medicine, Box 357650, Seattle, WA 98195 7650, USA
    J Virol 82:335-45. 2008
    ....
  11. ncbi FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress
    Zuzana Tothova
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Cell 128:325-39. 2007
    ..Thus, FoxO proteins play essential roles in the response to physiologic oxidative stress and thereby mediate quiescence and enhanced survival in the HSC compartment, a function that is required for its long-term regenerative potential...
  12. ncbi Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development
    V Brault
    Department of Molecular Embryology, Max Planck Institute of Immunobiology, Stuebeweg 51, D 79108 Freiburg, Germany
    Development 128:1253-64. 2001
    ..Our results demonstrate the pivotal role of beta-catenin in morphogenetic processes during brain and craniofacial development...
  13. ncbi The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells
    Kaoru Mitsui
    Laboratory of Animal Molecular Technology, Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Nara 630 0192, Japan
    Cell 113:631-42. 2003
    ..nanog-deficient ES cells lost pluripotency and differentiated into extraembryonic endoderm lineage. These data demonstrate that Nanog is a critical factor underlying pluripotency in both ICM and ES cells...
  14. pmc CD4(+)CD25(-)Foxp3(-) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis
    Charles F Anderson
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 204:285-97. 2007
    ....
  15. pmc A highly efficient recombineering-based method for generating conditional knockout mutations
    Pentao Liu
    Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA
    Genome Res 13:476-84. 2003
    ..This method should also facilitate the generation of knock-in mutations and transgene constructs, as well as expedite the analysis of regulatory elements and functional domains in or near genes...
  16. pmc Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting
    S Kersten
    Institut de Biologie Animale, Universite de Lausanne, CH 1015 Lausanne, Switzerland
    J Clin Invest 103:1489-98. 1999
    ..By modulating gene expression, PPARalpha stimulates hepatic fatty acid oxidation to supply substrates that can be metabolized by other tissues...
  17. pmc Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance
    Laura Bonifaz
    Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA
    J Exp Med 196:1627-38. 2002
    ..Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation...
  18. pmc Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata
    Filip K Swirski
    Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Clin Invest 117:195-205. 2007
    ..Conversely, the number of Ly-6C(lo) cells remained unaffected. Thus, we believe that Ly-6C(hi) monocytes represent a newly recognized component of the inflammatory response in experimental atherosclerosis...
  19. ncbi Pten is essential for embryonic development and tumour suppression
    A Di Cristofano
    Department of Human Genetics, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute, New York, NY 10021, USA
    Nat Genet 19:348-55. 1998
    ..These results support the notion that PTEN haploinsufficiency plays a causal role in CD, LDD and BZS pathogenesis, and demonstrate that Pten is a tumour suppressor essential for embryonic development...
  20. ncbi Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart
    Chen Leng Cai
    Institute of Molecular Medicine, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
    Dev Cell 5:877-89. 2003
    ..Our results have implications for the development of specific cardiac lineages, left-right asymmetry, cardiac evolution, and isolation of cardiac progenitor cells...
  21. ncbi A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome
    J Guy
    Wellcome Centre for Cell Biology, Institute of Cell and Molecular Biology, University of Edinburgh, The King s Buildings, Edinburgh, UK
    Nat Genet 27:322-6. 2001
    ....
  22. ncbi Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene
    M Elchebly
    Department of Biochemistry, McGill University, 3655 Drummond Street, Montreal, Quebec, Canada, H3G 1Y6
    Science 283:1544-8. 1999
    ..These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity...
  23. pmc Late developmental plasticity in the T helper 17 lineage
    Yun Kyung Lee
    Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Immunity 30:92-107. 2009
    ..These results support a model of late Th17 developmental plasticity with implications for autoimmunity and host defense...
  24. ncbi Transcriptional regulation by calcium, calcineurin, and NFAT
    Patrick G Hogan
    The Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 17:2205-32. 2003
  25. ncbi Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation
    R M Chemelli
    Howard Hughes Medical Institute, Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, 75235 9050, USA
    Cell 98:437-51. 1999
    ..Here, we report that, by behavioral and electroencephalographic criteria, orexin knockout mice exhibit a phenotype strikingly similar to human narcolepsy patients, as well as canarc-1 mutant dogs, the only ..
  26. pmc Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine
    Ivaylo I Ivanov
    Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA
    Cell Host Microbe 4:337-49. 2008
    ..Our results suggest that composition of intestinal microbiota regulates the Th17:Treg balance in the LP and may thus influence intestinal immunity, tolerance, and susceptibility to inflammatory bowel diseases...
  27. pmc MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity
    Hajime Kanda
    Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
    J Clin Invest 116:1494-505. 2006
    ..These findings suggest that an increase in MCP-1 expression in adipose tissue contributes to the macrophage infiltration into this tissue, insulin resistance, and hepatic steatosis associated with obesity in mice...
  28. pmc The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues
    T Lindsten
    Department of Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Cell 6:1389-99. 2000
    ..Thus, Bax and Bak have overlapping roles in the regulation of apoptosis during mammalian development and tissue homeostasis...
  29. ncbi IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo
    M M Fort
    DNAX Research Institute, Palo Alto, CA 94304, USA
    Immunity 15:985-95. 2001
    ..These results suggest that IL-25, derived from Th2 T cells, is capable of amplifying allergic type inflammatory responses by its actions on other cell types...
  30. ncbi Cancer immunoediting: from immunosurveillance to tumor escape
    Gavin P Dunn
    Department of Pathology and Immunology, Center for Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Nat Immunol 3:991-8. 2002
    ..In this review, we will summarize the historical and experimental basis of cancer immunoediting and discuss its dual roles in promoting host protection against cancer and facilitating tumor escape from immune destruction...
  31. ncbi Initial sequencing and comparative analysis of the mouse genome
    Robert H Waterston
    Genome Sequencing Center, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA
    Nature 420:520-62. 2002
    ....
  32. ncbi Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme
    M Muramatsu
    Department of Medical Chemistry, Graduate School of Medicine, Institute for Virus Research, Kyoto University, Japan
    Cell 102:553-63. 2000
    ..These results suggest that AID may be involved in regulation or catalysis of the DNA modification step of both class switching and somatic hypermutation...
  33. ncbi IRF-7 is the master regulator of type-I interferon-dependent immune responses
    Kenya Honda
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Nature 434:772-7. 2005
    ..Thus, all elements of IFN responses, whether the systemic production of IFN in innate immunity or the local action of IFN from plasmacytoid dendritic cells in adaptive immunity, are under the control of IRF-7...
  34. ncbi Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain
    Daniel J Cua
    Department of Immunology, DNAX Research Inc, Palo Alto, California 94304 1104, USA
    Nature 421:744-8. 2003
    ..In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages...
  35. ncbi A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection
    H Suzuki
    Chugai Pharmaceutical Co Ltd, Shizuoka, Japan
    Nature 386:292-6. 1997
    ..In addition, MSR-A-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1, ..
  36. ncbi Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock
    Thomas Vogl
    Institute of Experimental Dermatology, University of Munster, D 48129 Munster, Germany
    Nat Med 13:1042-9. 2007
    ..Therefore Mrp8-Mrp14 complexes are new inflammatory components that amplify phagocyte activation during sepsis upstream of TNFalpha-dependent effects...
  37. pmc Requirement for hippocampal CA3 NMDA receptors in associative memory recall
    Kazu Nakazawa
    Picower Center for Learning and Memory, RIKEN MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Science 297:211-8. 2002
    ..These results provide direct evidence for CA3 NMDA receptor involvement in associative memory recall...
  38. pmc Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene
    N Harada
    Banyu Tsukuba Research Institute Merck, Tsukuba 300 2611, Japan
    EMBO J 18:5931-42. 1999
    ..in the offspring intestines, which caused adenomatous intestinal polyps resembling those in Apc(Delta716) knockout mice. Some nascent microadenomas were also found in the colon...
  39. ncbi Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer
    Shunyou Wang
    Howard Hughes Medical Institute, University of California Los Angeles School of Medicine, 90095, Los Angeles, CA, USA
    Cancer Cell 4:209-21. 2003
    ..This murine prostate cancer model provides a unique tool for both exploring the molecular mechanism underlying prostate cancer and for development of new targeted therapies...
  40. pmc Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses
    Manish J Butte
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Immunity 27:111-22. 2007
    ..Our findings point to a substantial bidirectional inhibitory interaction between B7-1 and PD-L1 and add an additional dimension to immunoregulatory functions of the B7:CD28 family...
  41. ncbi Toll-like receptors control activation of adaptive immune responses
    M Schnare
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Nat Immunol 2:947-50. 2001
    ..These results suggest that distinct pathways of the innate immune system control activation of the two effector arms of adaptive immunity...
  42. ncbi Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
    J C Yoon
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 413:131-8. 2001
    ..These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver...
  43. pmc RANK is essential for osteoclast and lymph node development
    W C Dougall
    Immunex Corporation, Seattle, Washington 98101 USA
    Genes Dev 13:2412-24. 1999
    ..These experiments reveal that RANK provides critical signals necessary for lymph node organogenesis and osteoclast differentiation...
  44. ncbi Role of brain insulin receptor in control of body weight and reproduction
    J C Bruning
    Klinik II und Poliklinik für Innere Medizin and Center of Molecular Medicine ZMMK der Universität zu Köln, Joseph Stelzmann Strasse 9, 50931 Cologne, Germany
    Science 289:2122-5. 2000
    ..Thus, IR signaling in the CNS plays an important role in regulation of energy disposal, fuel metabolism, and reproduction...
  45. ncbi ATM and related protein kinases: safeguarding genome integrity
    Yosef Shiloh
    The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Rev Cancer 3:155-68. 2003
    ..Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers...
  46. pmc Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein
    P J Koch
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Cell Biol 151:389-400. 2000
    ....
  47. pmc Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes
    Jay D Horton
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    Proc Natl Acad Sci U S A 100:12027-32. 2003
    ....
  48. pmc 11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress
    Y Kotelevtsev
    Centre for Genome Research, University of Edinburgh, Kings Buildings, West Mains Road, Edinburgh EH 9 3JQ, Scotland, UK
    Proc Natl Acad Sci U S A 94:14924-9. 1997
    ..The 11beta-HSD-1 -/- mice were found to resist hyperglycamia provoked by obesity or stress. Attenuation of hepatic 11beta-HSD-1 may provide a novel approach to the regulation of gluconeogenesis...
  49. pmc Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy
    T Sullivan
    Advanced BioScience Laboratories Basic Research Program, National Cancer Institute Frederick Cancer Research and Development Center, Maryland 21702, USA
    J Cell Biol 147:913-20. 1999
    ..Mice lacking the A-type lamins exhibit tissue-specific alterations to their nuclear envelope integrity and emerin distribution. In skeletal and cardiac muscles, this is manifest as a dystrophic condition related to EDMD...
  50. ncbi Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin
    Andrew M Intlekofer
    Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Immunol 6:1236-44. 2005
    ..Therefore, these key transcription factors link the long-term renewal of memory CD8(+) T cells to their characteristic effector potency...
  51. ncbi Mitochondrial fusion protects against neurodegeneration in the cerebellum
    Hsiuchen Chen
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Cell 130:548-62. 2007
    ....
  52. ncbi A critical role for IL-21 in regulating immunoglobulin production
    Katsutoshi Ozaki
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Science 298:1630-4. 2002
    ..This suggests that these gammac-dependent cytokines may be those whose inactivation is primarily responsible for the B cell defect in humans with XSCID...
  53. ncbi RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems
    Koichi Kobayashi
    Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 416:194-9. 2002
    ..Rip2 is therefore a signal transducer and integrator of signals for both the innate and adaptive immune systems...
  54. pmc The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure
    Y Belkaid
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg 4 Rm 126, Center Dr MSC 0425, Bethesda, MD 20892, USA
    J Exp Med 194:1497-506. 2001
    ....
  55. ncbi Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2
    M Trommsdorff
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235 9046, USA
    Cell 97:689-701. 1999
    ..mDab1 expression is upregulated in knockout mice that lack both VLDLR and ApoER2...
  56. pmc TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis
    Andre Bafica
    Immunobiology Section, Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 202:1715-24. 2005
    ..by several major mycobacterial ligands, we analyzed the resistance of TLR9(-/-) as well as TLR2/9 double knockout mice to aerosol infection with Mycobacterium tuberculosis...
  57. pmc NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta
    Florian R Greten
    Second Department of Medicine, Klinikum rechts der Isar, Technical University Munich, 81675 Germany
    Cell 130:918-31. 2007
    ..These results unravel an unanticipated role for IKKbeta-dependent NF-kappaB signaling in the negative control of IL-1beta production and highlight potential complications of long-term IKKbeta inhibition...
  58. ncbi Identification of ubiquitin ligases required for skeletal muscle atrophy
    S C Bodine
    Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY, 10591 6707, USA
    Science 294:1704-8. 2001
    ..Overexpression of MAFbx in myotubes produced atrophy, whereas mice deficient in either MAFbx or MuRF1 were found to be resistant to atrophy. These proteins are potential drug targets for the treatment of muscle atrophy...
  59. ncbi Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis
    C J Sinal
    Laboratory of Metabolism, Division of Basic Sciences, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell 102:731-44. 2000
    ..These data demonstrate that FXR/BAR is critical for bile acid and lipid homeostasis by virtue of its role as an intracellular bile acid sensor...
  60. ncbi Natural regulatory T cells control the development of atherosclerosis in mice
    Hafid Ait-Oufella
    Institut National de la Sante et de la Recherche Medicale INSERM, Unit 689, Centre de Recherché Cardiovasculaire Lariboisière, 41, Bd de la Chapelle, 75010 Paris, France
    Nat Med 12:178-80. 2006
    ..These results provide new insights into the immunopathogenesis of atherosclerosis and could lead to new therapeutic approaches that involve immune modulation using regulatory T cells...
  61. pmc IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response
    Kyungho Lee
    Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Genes Dev 16:452-66. 2002
    ..Both processing of ATF6 and IRE1alpha-mediated splicing of XBP1 mRNA are required for full activation of the UPR...
  62. pmc Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity
    Tao Ren
    Genetics Department, Harvard Medical School, Boston, Massachusetts, USA
    PLoS Pathog 2:e18. 2006
    ..It thus appears that macrophages sense cytosolic flagellin via a TLR5-independent pathway that leads to rapid caspase-1-dependent cell death and provides defense against intracellular bacterial pathogens...
  63. pmc The knockout mouse project
    Christopher P Austin
    National Human Genome Research Institute, National Institutes of Health, Building 31, Room 4B09, 31 Center Drive, Bethesda, Maryland 20892, USA
    Nat Genet 36:921-4. 2004
    ..It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain...
  64. ncbi Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice
    L Gu
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Mol Cell 2:275-81. 1998
    ..Thus, MCP-1 plays a unique and crucial role in the initiation of atherosclerosis and may provide a new therapeutic target in this disorder...
  65. ncbi Dicer is essential for mouse development
    Emily Bernstein
    Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nat Genet 35:215-7. 2003
    ..Coupled with our inability to generate viable Dicer1-null embryonic stem (ES) cells, this suggests a role for Dicer, and, by implication, the RNAi machinery, in maintaining the stem cell population during early mouse development...
  66. ncbi DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development
    M Okano
    Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Charlestown 02129, USA
    Cell 99:247-57. 1999
    ..Our results indicate that both Dnmt3a and Dnmt3b function as de novo methyltransferases that play important roles in normal development and disease...
  67. ncbi Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Annu Rev Pharmacol Toxicol 47:89-116. 2007
    ..The development of Nrf2 knockout mice has provided key insights into the toxicological importance of this pathway...
  68. ncbi Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
    Mehrdad Matloubian
    Howard Hughes Medical Institute and Department of Microbiology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143 0414, USA
    Nature 427:355-60. 2004
    ..These findings establish that S1P1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs...
  69. ncbi Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf
    Amal Amer
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 281:35217-23. 2006
    ..These results reveal that Ipaf restricts Legionella replication through the regulation of phagosome maturation, providing a novel function for NLR proteins in host defense against an intracellular bacterium...
  70. pmc Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection
    Ari B Molofsky
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Exp Med 203:1093-104. 2006
    ..Accordingly, macrophages respond to cytosolic flagellin by a mechanism that requires Naip5 and caspase 1 to restrict bacterial replication and release proinflammatory cytokines that control L. pneumophila infection...
  71. ncbi NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells
    Mamoru Ito
    Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University, 1430 Nogawa, Miyamae, Kawasaki, Kanagawa 216 0001, Japan
    Blood 100:3175-82. 2002
    ....
  72. ncbi Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta
    T Nakagawa
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 403:98-103. 2000
    ..Thus, caspase-12 mediates an ER-specific apoptosis pathway and may contribute to amyloid-beta neurotoxicity...
  73. pmc Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis
    David R Beers
    Department of Neurology, Methodist Neurological Institute, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 103:16021-6. 2006
    ..This study confirms the importance of microglia as a double-edged sword, and focuses on the importance of targeting microglia to minimize cytotoxicity and maximize neuroprotection in neurodegenerative diseases...
  74. ncbi Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4-methylenedioxymethamphetamine ("Ecstasy") in serotonin transporter-deficient mice
    D Bengel
    Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20892 1264, USA
    Mol Pharmacol 53:649-55. 1998
    ..Together, these data suggest that the presence of a functional 5-HTT is essential for brain 5-HT homeostasis and for 3,4-methylenedioxymethamphetamine-induced hyperactivity...
  75. ncbi Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption
    Scott W Altmann
    Department of Cardiovascular Endocrine Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ, 07033 0539, USA
    Science 303:1201-4. 2004
    ..Ezetimibe, a drug that inhibits cholesterol absorption, had no effect in NPC1L1 knockout mice, suggesting that NPC1L1 resides in an ezetimibe-sensitive pathway responsible for intestinal cholesterol ..
  76. ncbi TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells
    Marc Veldhoen
    Division of Molecular Immunology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    Immunity 24:179-89. 2006
    ..Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells...
  77. pmc Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility
    K G Danielson
    Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Cell Biol 136:729-43. 1997
    ..These findings demonstrate a fundamental role for decorin in regulating collagen fiber formation in vivo...
  78. ncbi IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge
    Shabaana A Khader
    Trudeau Institute, Saranac Lake, New York 12983, USA
    Nat Immunol 8:369-77. 2007
    ....
  79. ncbi Defective membrane repair in dysferlin-deficient muscular dystrophy
    Dimple Bansal
    Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa 52242, USA
    Nature 423:168-72. 2003
    ..Our findings show that disruption of the muscle membrane repair machinery is responsible for dysferlin-deficient muscle degeneration, and highlight the importance of this basic cellular mechanism of membrane resealing in human disease...
  80. ncbi Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells
    Keisuke Ito
    Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinano machi, Shinjuku ku, Tokyo 160 8582, Japan
    Nature 431:997-1002. 2004
    ..These results show that the self-renewal capacity of HSCs depends on ATM-mediated inhibition of oxidative stress...
  81. pmc SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
    Jay D Horton
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Clin Invest 109:1125-31. 2002
  82. pmc Disrupted cortical map and absence of cortical barrels in growth-associated protein (GAP)-43 knockout mice
    D L Maier
    Department of Anatomy and Cell Biology, State University of New York Health Science Center, Syracuse, NY 13210, USA
    Proc Natl Acad Sci U S A 96:9397-402. 1999
    ..Our results indicate that GAP-43 expression is critical for the normal establishment of ordered topography in barrel cortex...
  83. pmc DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes
    Satomi Kuramochi-Miyagawa
    Department of Pathology, Medical School, Graduate School of Frontier Biosciences, Research Institute for Microbial Diseases, Osaka University, Yamada oka 2 2 Suita, Osaka 565 0871, Japan
    Genes Dev 22:908-17. 2008
    ..Our data strongly suggest that MILI and MIWI2 play essential roles in establishing de novo DNA methylation of retrotransposons in fetal male germ cells...
  84. pmc Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice
    Fumihiko Ishikawa
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney St, no 770, Boston, MA 02115, USA
    Blood 106:1565-73. 2005
    ..Thus, the NOD/SCID/IL2rgamma(null) newborn system might be an important experimental model to study the human hemato-lymphoid system...
  85. pmc The drusenlike phenotype in aging Ccl2-knockout mice is caused by an accelerated accumulation of swollen autofluorescent subretinal macrophages
    Ulrich F O Luhmann
    Department of Genetics, UCL Institute of Ophthalmology, London, United Kingdom
    Invest Ophthalmol Vis Sci 50:5934-43. 2009
    ..This study was conducted to investigate the nature of the drusenlike lesions in vivo and further evaluate the Ccl2(-/-) mouse as a model of AMD...
  86. ncbi Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment
    M Romano
    Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy
    Immunity 6:315-25. 1997
    ..Hence, in vivo and in vitro evidence supports the concept that the IL-6 system plays an unexpected positive role in local inflammatory reactions by amplifying leukocyte recruitment...
  87. pmc CD8+ T cells mediate recovery and immunopathology in West Nile virus encephalitis
    Yang Wang
    Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University, Canberra ACT 2601, Australia
    J Virol 77:13323-34. 2003
    ..Using high doses of virus in CD8-deficient mice leads to increased survival. These results provide evidence that CD8(+) T cells are involved in both recovery and immunopathology in WNV infection...
  88. pmc Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency
    A Yachie
    Department of Laboratory Sciences, School of Health Sciences, Kanazawa University, Japan
    J Clin Invest 103:129-35. 1999
    ..This study presents not only the first human case of HO-1 deficiency but may also provide clues to the key roles played by this important enzyme in vivo...
  89. ncbi Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components
    O Takeuchi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan
    Immunity 11:443-51. 1999
    ..These results demonstrate that TLR2 and TLR4 recognize different bacterial cell wall components in vivo and TLR2 plays a major role in Gram-positive bacterial recognition...
  90. pmc The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo
    Mandy J McGeachy
    Schering Plough Biopharma, Palo Alto, California 94304, USA
    Nat Immunol 10:314-24. 2009
    ..These defects were associated with less proliferation; consequently, fewer effector T(H)-17 cells were produced in the lymph nodes and hence available to emigrate to the bloodstream and tissues...
  91. ncbi Divergence of melanocortin pathways in the control of food intake and energy expenditure
    Nina Balthasar
    Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA
    Cell 123:493-505. 2005
    ..Disassociation of food intake and energy expenditure reveals unexpected divergence in melanocortin pathways controlling energy balance...
  92. ncbi Emerging roles of secreted phospholipase A2 enzymes: Lessons from transgenic and knockout mice
    Makoto Murakami
    Biomembrane Signaling Project, The Tokyo Metropolitan Institute of Medical Science, 2 1 6 Kamikitazawa, Setagaya Ku, Tokyo 156 8506, Japan
    Biochimie 92:561-82. 2010
    ..Recent studies using transgenic and knockout mice for several sPLA(2) enzymes, in combination with lipidomics approaches, have opened new insights into their ..
  93. pmc Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice
    Masaaki Komatsu
    Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
    J Cell Biol 169:425-34. 2005
    ..Here, we generated conditional knockout mice of Atg7, an essential gene for autophagy in yeast...
  94. ncbi Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases
    Hideaki Kamata
    Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Cell 120:649-61. 2005
    ..Antioxidant treatment also prevents TNFalpha-mediated fulminant liver failure without affecting liver regeneration...
  95. ncbi Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice
    K Kovalovich
    Department of Genetics, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
    Hepatology 31:149-59. 2000
    ..These data provide evidence for an important role for IL-6 in reducing CCl(4)-induced acute and chronic liver injury and fibrosis...
  96. ncbi Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence
    L M Bohn
    Howard Hughes Medical Institute Laboratories, Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 408:720-3. 2000
    ..However, the deletion of beta-arrestin-2 does not prevent the chronic morphine-induced up-regulation of adenylyl cyclase activity, a cellular marker of dependence, and the mutant mice still become physically dependent on the drug...
  97. ncbi Toll-like receptors modulate adult hippocampal neurogenesis
    Asya Rolls
    Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel
    Nat Cell Biol 9:1081-8. 2007
    ..Thus, our study identified TLRs as players in adult neurogenesis and emphasizes their specified and diverse role in cell renewal...
  98. doi Transcriptional paradigms in mammalian mitochondrial biogenesis and function
    Richard C Scarpulla
    Department of Cell and Molecular Biology, Northwestern Medical School, Chicago, Illinois 60611, USA
    Physiol Rev 88:611-38. 2008
    ..These transcriptional paradigms provide a basic framework for understanding the integration of mitochondrial biogenesis and function with signaling events that dictate cell- and tissue-specific energetic properties...
  99. ncbi Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis
    Tian Wang
    Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, Connecticut 06520, USA
    Nat Med 10:1366-73. 2004
    ..Collectively, WNV infection leads to a Tlr3-dependent inflammatory response, which is involved in brain penetration of the virus and neuronal injury...
  100. ncbi Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha
    D J Peet
    Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 75235 9050, USA
    Cell 93:693-704. 1998
    ..These results demonstrate the existence of a physiologically significant feed-forward regulatory pathway for sterol metabolism and establish the role of LXR alpha as the major sensor of dietary cholesterol...
  101. pmc Elevated matrix metalloprotease and angiostatin levels in integrin alpha 1 knockout mice cause reduced tumor vascularization
    A Pozzi
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 97:2202-7. 2000
    ..Integrin alpha1-deficient mice thus provide a genetically characterized model for enhanced angiostatin production and serve to reveal an unwanted potential side effect of MMP inhibition, increased tumor angiogenesis...

Research Grants89

  1. Discovery metabolite profiling of the prolyl peptidases
    Alan Saghatelian; Fiscal Year: 2009
    ..Furthermore, the application of DMP to peptidases will demonstrate the generality of this approach for the future characterization of medically relevant enzymes and signaling pathways. ..
  2. Cardiac Physiology and Imaging Core for Mouse in Vivo
    Kirk Peterson; Fiscal Year: 2009
    ..The microvideoangiographic approach has also been used to demonstrate pronounced aortic tortuosity in DANCE knockout mice, Figure 21. Figure 21: Tortuous aorta in DANCE-deficient mice...
  3. Understanding the Cognitive Impact of Early Life Epilepsy
    Frances Jensen; Fiscal Year: 2009
    ..abstract_text> ..
  4. Biomedical Simulations Resource (BMSR)
    DAVID Z D apos ARGENIO; Fiscal Year: 2010
    ..05/01) Page Biographical Sketch Format Page ..
  5. Biomedical Simulations Resource (BMSR)
    DAVID D ARGENIO; Fiscal Year: 2009
    ..05/01) Page Biographical Sketch Format Page ..
  6. Duke Comp Cancer Inst. Core Support Grant
    HERBERT KIM LYERLY; Fiscal Year: 2010
    ..A cancer focus is illustrated by $2,991,535 or 11.3% of funding from the NCI, the American Cancer Society or the Department of Defense. ..
  7. Molecular Biology Core Laboratory
    David Russell; Fiscal Year: 2009
    ..determination of tissue-specific expression patterns of genes under study via immunoblotting in transgenic and knockout mice is heavily dependent on this aspect of the Core...
  8. MOLECULAR & CELLULAR MECHANISMS IN TRANSFUSION MEDICINE
    Peter J Newman; Fiscal Year: 2011
    ....
  9. Gamma-Synuclein-Mediated Regulation of Norepinephrine Transporter
    Anita Sidhu; Fiscal Year: 2009
    ..This grant is also relevant for the ARRA in that it will immediately create 3 new professional jobs. ..
  10. Gamma-Synuclein-Mediated Regulation of Norepinephrine Transporter
    Anita Sidhu; Fiscal Year: 2010
    ..This grant is also relevant for the ARRA in that it will immediately create 3 new professional jobs. ..
  11. Pyruvate Dehydrogenase kinase as Therapeutic Target for Hepatic Steatosis, Obesit
    Robert Harris; Fiscal Year: 2009
    ..The immediate objective is to perform proof-of- principle studies with PDK knockout mice generated in my laboratory...
  12. Regulation of Opioid Signaling by Tyr-Phosphorylation
    Charles Chavkin; Fiscal Year: 2009
    ..The role of InternaliSiiation Ih preventing JNK-mediated inaottyatlon Wl|j be assessed by using 0RK3 knockout mice . to prevent fentanyi-lnduced'Internalization of MOR...
  13. Role of murine induced pluripotent stem cells on the correction of cardiac and sk
    Diego Fraidenraich; Fiscal Year: 2009
    ..Using a mouse model of the "thin myocardial syndrome" (Id knockout mice), we have shown that secreted factors from ES cells normalize gene expression profiles in neighbor cells...
  14. Role of murine induced pluripotent stem cells on the correction of cardiac and sk
    Diego Fraidenraich; Fiscal Year: 2010
    ..Using a mouse model of the "thin myocardial syndrome" (Id knockout mice), we have shown that secreted factors from ES cells normalize gene expression profiles in neighbor cells...
  15. The wnt signaling pathway in choroidal neovascularization
    Jian Xing Ma; Fiscal Year: 2009
    ..Our recent studies showed that VLDLR knockout mice develop typical CNV, and manifest most abnormalities of human AMD such as retinal inflammation, vascular ..
  16. Role and Mechanisms of Prolactin on HPA Axis Activation Following Stress
    James Janik; Fiscal Year: 2009
    ..i) post- partum, female wild-type mice (physiologically hyperprolactinemic) or (ii) wild-type and PRL knockout mice treated with exogenous PRL to induce hyperprolactinemia for 1, 3 or 6 days to determine the time course and ..
  17. The Pharmacology of Dermal Fibrosis
    Bruce Cronstein; Fiscal Year: 2009
    ..diffuse dermal fibrosis induced by bleomycin treatment in wild type, adenosine A1, A2A, A2B and A3 receptor knockout mice, mice that generate less extracellular adenosine (ecto-5'Nucleotidase and nucleoside triphosphate ..
  18. Lipoic Acid Therapy for Experimental Autoimmune Encephalomyelitis
    Dennis Bourdette; Fiscal Year: 2009
    ..Current FDA approved therapies for MS cost up to $35,000 a year and are only partially effective. Finding new, cost effective therapies that can slow the progression of MS is of obvious relevance to the health care mission of VHA. ..
  19. Probiotic-Induced Elimination of Oxalate to Treat Hyperoxaluria Associated with P
    Marguerite Hatch; Fiscal Year: 2010
    ....
  20. The genetics and pathophysiology of impaired Wnt signaling in metabolic syndrome
    Arya Mani; Fiscal Year: 2009
    ..Preliminary results from IPGTT in heterozygote knockout mice on Western diet has demonstrated increased glucose stimulated insulin levels and reduced hepatic glycogen ..
  21. The genetics and pathophysiology of impaired Wnt signaling in metabolic syndrome
    Arya Mani; Fiscal Year: 2010
    ..Preliminary results from IPGTT in heterozygote knockout mice on Western diet has demonstrated increased glucose stimulated insulin levels and reduced hepatic glycogen ..
  22. Targeting S1P receptors to prevent hearing loss
    Jerold Chun; Fiscal Year: 2009
    ..This will be approached by careful analysis of knockout mice for each S1P receptor subtype...
  23. REGULATION OF CELLULAR RESPONSES TO NEUROPEPTIDES
    Nigel Bunnett; Fiscal Year: 2009
    ..will be examined by expression of dominant negative mutants, and by studying neurons from p- arrestin knockout mice. The role of the cytoskeleton and of endosomal acidification and phosphatases will be examined using specific ..
  24. REGULATION OF CELLULAR RESPONSES TO NEUROPEPTIDES
    Nigel W Bunnett; Fiscal Year: 2010
    ..will be examined by expression of dominant negative mutants, and by studying neurons from p- arrestin knockout mice. The role of the cytoskeleton and of endosomal acidification and phosphatases will be examined using specific ..
  25. REGULATION OF CELLULAR RESPONSES TO NEUROPEPTIDES
    Nigel Bunnett; Fiscal Year: 2007
    ..will be examined by expression of dominant negative mutants, and by studying neurons from p- arrestin knockout mice. The role of the cytoskeleton and of endosomal acidification and phosphatases will be examined using specific ..
  26. Role of G-gamma-7 in striatal cannabinoid and D2 dopamine
    Dana Selley; Fiscal Year: 2009
    ..Our preliminary findings indicate that AC inhibition by striatal CB1 and D2 receptors is diminished in Gng7 knockout mice, suggesting a role for this G-gamma subunit in inhibitory Gi/o signaling...
  27. Role of G-gamma-7 in striatal cannabinoid and D2 dopamine
    Dana E Selley; Fiscal Year: 2010
    ..Our preliminary findings indicate that AC inhibition by striatal CB1 and D2 receptors is diminished in Gng7 knockout mice, suggesting a role for this G-gamma subunit in inhibitory Gi/o signaling...
  28. Resistance of Beta 2 Microglobulin Null Mice to Sepsis
    Edward Sherwood; Fiscal Year: 2009
    Beta2 microglobulin knockout mice are deficient in CD8+ T cells and natural killer T cells...
  29. Resistance of Beta 2 Microglobulin Null Mice to Sepsis
    Edward Sherwood; Fiscal Year: 2003
    Beta2 microglobulin knockout mice are deficient in CD8+ T cells and natural killer T cells...
  30. Resistance of Beta 2 Microglobulin Null Mice to Sepsis
    Edward Sherwood; Fiscal Year: 2004
    Beta2 microglobulin knockout mice are deficient in CD8+ T cells and natural killer T cells...
  31. Resistance of Beta 2 Microglobulin Null Mice to Sepsis
    Edward Sherwood; Fiscal Year: 2006
    unreadable] DESCRIPTION (provided by applicant): [unreadable] Beta2 microglobulin knockout mice are deficient in CD8+ T cells and natural killer T cells...
  32. Resistance of Beta 2 Microglobulin Null Mice to Sepsis
    Edward Sherwood; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): [unreadable] Beta2 microglobulin knockout mice are deficient in CD8+ T cells and natural killer T cells...
  33. Resistance of Beta 2 Microglobulin Null Mice to Sepsis
    Edward Sherwood; Fiscal Year: 2005
    Beta2 microglobulin knockout mice are deficient in CD8+ T cells and natural killer T cells...
  34. Anxiety development in 5-HT1A autoreceptor knockout mice, interaction with stress
    Rene Hen; Fiscal Year: 2010
    ....
  35. Anxiety development in 5-HT1A autoreceptor knockout mice, interaction with stress
    Sheryl Beck; Fiscal Year: 2009
    ....
  36. Regulation and Function of Cytosolic Phospholipases A2 in Lung Cells
    CHRISTINA CARROLL LESLIE; Fiscal Year: 2010
    ..Eicosanoid production is not completely ablated in cPLA2a knockout mice or in cPLA2a-deficient lung fibroblasts...
  37. X-RAYS INDUCE EXOCYTOSIS OF ENDOTHELIAL P-SELECTIN
    Dennis Hallahan; Fiscal Year: 1999
    ..We will study the roles of calcium and calmodulin in the activation of motor proteins that are required for microtubule- dependent translocation of WPB to the cell membrane. ..
  38. Regulation and Function of Cytosolic Phospholipases A2 in Lung Cells
    Christina Leslie; Fiscal Year: 2009
    ..Eicosanoid production is not completely ablated in cPLA2a knockout mice or in cPLA2a-deficient lung fibroblasts...
  39. X-RAYS INDUCE EXOCYTOSIS OF ENDOTHELIAL P-SELECTIN
    Dennis Hallahan; Fiscal Year: 2001
    ..We will study the roles of calcium and calmodulin in the activation of motor proteins that are required for microtubule- dependent translocation of WPB to the cell membrane. ..
  40. X-RAYS INDUCE EXOCYTOSIS OF ENDOTHELIAL P-SELECTIN
    Dennis Hallahan; Fiscal Year: 2002
    ..We will study the roles of calcium and calmodulin in the activation of motor proteins that are required for microtubule- dependent translocation of WPB to the cell membrane. ..
  41. X-RAYS INDUCE EXOCYTOSIS OF ENDOTHELIAL P-SELECTIN
    Dennis Hallahan; Fiscal Year: 2000
    ..We will study the roles of calcium and calmodulin in the activation of motor proteins that are required for microtubule- dependent translocation of WPB to the cell membrane. ..
  42. PHYSICOCHEMICAL INVESTIGATION OF TASTE
    John DeSimone; Fiscal Year: 2007
    ..Preliminary data from NADPH oxidase knockout mice indicate that protons cross the apical membranes of taste cells through two hydrogen ion channels...
  43. PHYSICOCHEMICAL INVESTIGATION OF TASTE
    John DeSimone; Fiscal Year: 2006
    ..Preliminary data from NADPH oxidase knockout mice indicate that protons cross the apical membranes of taste cells through two hydrogen ion channels...
  44. PHYSICOCHEMICAL INVESTIGATION OF TASTE
    Vijay Lyall; Fiscal Year: 2009
    ..Preliminary data from NADPH oxidase knockout mice indicate that protons cross the apical membranes of taste cells through two hydrogen ion channels...
  45. PHYSICOCHEMICAL INVESTIGATION OF TASTE
    Vijay Lyall; Fiscal Year: 2010
    ..Preliminary data from NADPH oxidase knockout mice indicate that protons cross the apical membranes of taste cells through two hydrogen ion channels...
  46. CB1 Receptor Regulation by Cannabinoid Receptor Interacting Protein CRIP1a
    Dana Selley; Fiscal Year: 2009
    ..A CRIP1a gene knockout mouse line will be created using a "flox" approach. Knockout mice will be subjected to basic health assessment and in vivo phenotyping, followed by determination of effects of ..
  47. Dual role of the bradykinin B2 receptor during inflammation
    Bruce L Zuraw; Fiscal Year: 2011
    ..key questions: 1) What is/are the mechanism(s) that underlie the enhanced allergic airway inflammation in B2R knockout mice? 2) Is it possible to separate the pro- and anti-inflammatory effects of B2R inhibition in a temporal-spatial ..
  48. Mechanisms of Fatty Acid Induced Insulin Resistance
    Gerald Shulman; Fiscal Year: 2003
    ..high-fat feeding on insulin action and signaling in skeletal muscle will be examined in PKC? and Jun kinase 1 knockout mice. To test the hypothesis that accumulation of intramyocellular fatty acid metabolites are responsible for ..
  49. Mechanisms of Fatty Acid Induced Insulin Resistance
    Gerald Shulman; Fiscal Year: 2006
    ..high-fat feeding on insulin action and signaling in skeletal muscle will be examined in PKC? and Jun kinase 1 knockout mice. To test the hypothesis that accumulation of intramyocellular fatty acid metabolites are responsible for ..
  50. Cholinesterase Inhibitors in Alzheimer's Disease
    Debomoy Lahiri; Fiscal Year: 2009
    ..3] To examine the role of ChE enzyme in AChE knockout mice. We will study the role of the AChE enzyme on APP, AB peptides and synaptic protein markers in the brain ..
  51. POMC Processing and Beta-Endorphin-Related Opioid Peptides
    Vivian Hook; Fiscal Year: 2007
    ..vesicle cathepsin L as a key processing enzyme for POMC, based on exciting new results from cathepsin L knockout mice showing reduced levels of beta-endorphin...
  52. POMC Processing Beta-Endorphin-Related Opioid Peptides
    Vivian Hook; Fiscal Year: 2006
    ..vesicle cathepsin L as a key processing enzyme for POMC, based on exciting new results from cathepsin L knockout mice showing reduced levels of beta-endorphin...
  53. Effect of Bone Marrow Cells on the Radiosensitivity of Brain and Mouth Cancers
    John Brown; Fiscal Year: 2009
    ..and human GBM implanted intracranially and the FaDu human head and neck tumor inplanted subcutaneously in Rag1 knockout mice respectively...
  54. Transgenic/Molecular Approaches for Ocular Albinism
    Debora Farber; Fiscal Year: 2006
    ..Three different Gi protein knockout mice will also be examined to define the Gi protein through which OA1 normally functions, and constitutively active ..
  55. Transgenic/Molecular Approaches for Ocular Albinism
    Debora Farber; Fiscal Year: 2003
    ..Three different Gi protein knockout mice will also be examined to define the Gi protein through which OA1 normally functions, and constitutively active ..
  56. Transgenic/Molecular Approaches for Ocular Albinism
    Debora Farber; Fiscal Year: 2005
    ..Three different Gi protein knockout mice will also be examined to define the Gi protein through which OA1 normally functions, and constitutively active ..
  57. Transgenic/Molecular Approaches for Ocular Albinism
    Debora Farber; Fiscal Year: 2004
    ..Three different Gi protein knockout mice will also be examined to define the Gi protein through which OA1 normally functions, and constitutively active ..
  58. Adenosine Receptor Function in Bladder Uroepithelium
    Gerard Apodaca; Fiscal Year: 2009
    ..Selective inhibitors of enzymes/transporters as well as knockout mice lacking expression of adenosine kinase and adenosine deaminase will be used to define the mechanisms of ..
  59. Adenosine Receptor Function in Bladder Uroepithelium
    Gerard L Apodaca; Fiscal Year: 2011
    ..Selective inhibitors of enzymes/transporters as well as knockout mice lacking expression of adenosine kinase and adenosine deaminase will be used to define the mechanisms of ..
  60. Adenosine Receptor Function in Bladder Uroepithelium
    Gerard L Apodaca; Fiscal Year: 2010
    ..Selective inhibitors of enzymes/transporters as well as knockout mice lacking expression of adenosine kinase and adenosine deaminase will be used to define the mechanisms of ..
  61. Role of microRNA-122 in hepatocarcinogenesis using conditional knock out mice
    Kalpana Ghoshal; Fiscal Year: 2011
    ..the biological functions of miR-122, especially in hepatocarcinogenesis, we have generated conditional knockout mice (supported by an R21 grant to the PI)...
  62. Role of microRNA-122 in hepatocarcinogenesis using conditional knock out mice
    Kalpana Ghoshal; Fiscal Year: 2010
    ..the biological functions of miR-122, especially in hepatocarcinogenesis, we have generated conditional knockout mice (supported by an R21 grant to the PI)...
  63. Regulation of Nucleotide Excision Repair by Proteolysis
    Pengbo Zhou; Fiscal Year: 2010
    ..Importantly, we generated conditional CUL-4A knockout mice and showed that skin-specific CUL-4A knockout mice were resistant to UV-induced skin carcinogenesis, ..
  64. Regulation of Nucleotide Excision Repair by Proteolysis
    Pengbo Zhou; Fiscal Year: 2009
    ..Importantly, we generated conditional CUL-4A knockout mice and showed that skin-specific CUL-4A knockout mice were resistant to UV-induced skin carcinogenesis, ..
  65. NEUROCHEMICAL ACTIONS OF PSYCHOTROPIC DRUGS
    Solomon H Snyder; Fiscal Year: 2010
    ..We propose studies with Rhes knockout mice to elucidate its normal function and will cross-breed these animals with HD mice to evaluate potential ..
  66. GM-CSF is required for macrophage surfactant catabolism
    Tracey Bonfield; Fiscal Year: 2005
    ..abstract_text> ..
  67. Calcium Signaling, Metabolism, and EC Coupling in Heart
    Joshua I Goldhaber; Fiscal Year: 2011
    ..This will lead to new therapeutic strategies for preserving heart muscle function, thereby reducing the incidence of heart failure. ..
  68. CORE--TISSUE CULTURE AND MONOCLONAL ANTIBODIES
    MARY MICHAELIS; Fiscal Year: 2001
    ..such as cell cultures, including cells transfected with foreign genes and cells derived from transgenic and knockout mice. Advances in understanding the mechanisms for the biochemical pathology of diseases that lead to mental ..
  69. Calcium Signaling, Metabolism, and EC Coupling in Heart
    Joshua I Goldhaber; Fiscal Year: 2010
    ..This will lead to new therapeutic strategies for preserving heart muscle function, thereby reducing the incidence of heart failure. ..
  70. GM-CSF is required for macrophage surfactant catabolism
    Tracey Bonfield; Fiscal Year: 2003
    ..abstract_text> ..
  71. Calcium Signaling, Metabolism, and EC Coupling in Heart
    JOSHUA GOLDHABER; Fiscal Year: 2009
    ..This will lead to new therapeutic strategies for preserving heart muscle function, thereby reducing the incidence of heart failure. ..
  72. GM-CSF is required for macrophage surfactant catabolism
    Tracey Bonfield; Fiscal Year: 2006
    ..abstract_text> ..
  73. GM-CSF is required for macrophage surfactant catabolism
    Tracey Bonfield; Fiscal Year: 2006
    ..abstract_text> ..
  74. GM-CSF is required for macrophage surfactant catabolism
    Tracey Bonfield; Fiscal Year: 2004
    ..abstract_text> ..
  75. ROLE OF CSF-1 IN OSTEOCLAST FUNCTION
    Karl Insogna; Fiscal Year: 2009
    ..However, quite unexpectedly, we also found a profound disturbance in osteoblast function in LIM kinase-1 knockout mice with a nearly 40% reduction in osteoblast activity as judged by histomorphometry and in vitro mineralization ..
  76. Cholinesterase Inhibitors in Alzheimer's Disease
    Debomoy K Lahiri; Fiscal Year: 2010
    ..3] To examine the role of ChE enzyme in AChE knockout mice. We will study the role of the AChE enzyme on APP, AB peptides and synaptic protein markers in the brain ..
  77. Canonical Transient Receptor Potential (TRPC) subfamily function in Hippocampus.
    David E Clapham; Fiscal Year: 2010
    ..TRPC4, TRPC5, both TRPC4 and TRPC5 genes, obtained the TRPC1 knockout mouse, and are breeding TRPC1/4/5 triple knockout mice. Here we propose to use these mice to understand the function of these ion channels in the hippocampus using ..
  78. MUCOSAL IMMUNOLOGY OF HELICOBACTER INDUCED GASTRITIS
    Steven Czinn; Fiscal Year: 2007
    ..we have demonstrated that IFNy is the dominant cytokine associated with protective immunity but that IFNy-knockout mice can still be protectively immunized...
  79. Galanin-opiate interactions
    MARINA PICCIOTTO; Fiscal Year: 2009
    ..We have found that galanin knockout mice show increased morphine-induced locomotion and conditioned place preference (CPP), and that these behavioral ..
  80. Gq-coupled Receptors Inhibit PI 3-kinase/Akt Signaling Pathway
    Richard Lin; Fiscal Year: 2009
    ..activates mammalian target of rapamycin (mTOR) signaling in myotubes prepared from muscle-specific p110a knockout mice. IGF-1 activation of PI3K and then mTOR is thought to be a central regulatory signal for stimulating muscle ..
  81. PREVENTION OF QUINONE TOXICITY AND MUTAGENICITY
    ANIL JAISWAL; Fiscal Year: 2007
    ..NQO1-/- and NQO2-/- mice were cross-bred to generate double knockout mice deficient in both NQO1 and NQO2...
  82. PREVENTION OF QUINONE TOXICITY AND MUTAGENICITY
    ANIL JAISWAL; Fiscal Year: 2005
    ..NQO1-/- and NQO2-/- mice were cross-bred to generate double knockout mice deficient in both NQO1 and NQO2...
  83. PREVENTION OF QUINONE TOXICITY AND MUTAGENICITY
    ANIL JAISWAL; Fiscal Year: 2009
    ..NQO1-/- and NQO2-/- mice were cross-bred to generate double knockout mice deficient in both NQO1 and NQO2...
  84. PREVENTION OF QUINONE TOXICITY AND MUTAGENICITY
    ANIL JAISWAL; Fiscal Year: 2006
    ..NQO1-/- and NQO2-/- mice were cross-bred to generate double knockout mice deficient in both NQO1 and NQO2...
  85. Cbl-b in osteoclast function
    Archana Sanjay; Fiscal Year: 2003
    ..These features of Cbl knockout mice have therefore raised the possibility that c-Cbl and Cbl-b regulate different signaling pathways, a fact ..
  86. Undercarboxylated osteocalcin, body fat, and diabetes in older adults
    Ann Schwartz; Fiscal Year: 2009
    ..This research project will determine if lower ucOC levels predict development of diabetes or increases in total body fat over nine years. ..
  87. PAHs: Balance of Detoxication vs Metabolic Activation
    Daniel Nebert; Fiscal Year: 2009
    ..Using Cyp1a1(-/-) and Cyp1b1(-/-) knockout mice, we have shown that CYP1A1 is more important in detoxication than metabolic activation, whereas CYP1B1 causes ..
  88. PAHs: Balance of Detoxication vs Metabolic Activation
    Daniel Nebert; Fiscal Year: 2006
    ..Using Cyp1a1(-/-) and Cyp1b1(-/-) knockout mice, we have shown that CYP1A1 is more important in detoxication than metabolic activation, whereas CYP1B1 causes ..
  89. PAHs: Balance of Detoxication vs Metabolic Activation
    Daniel Nebert; Fiscal Year: 2009
    ..Using Cyp1a1(-/-) and Cyp1b1(-/-) knockout mice, we have shown that CYP1A1 is more important in detoxication than metabolic activation, whereas CYP1B1 causes ..