tight skin

Summary

Gene Symbol: tight skin
Description: fibrillin 1
Alias: AI536462, B430209H23, Fib-1, Tsk, fibrillin-1, tight skin
Species: mouse

Top Publications

  1. ncbi B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis
    Minoru Hasegawa
    Department of Dermatology, Kanazawa University Graduate School of Medical Science, Japan
    Am J Pathol 169:954-66. 2006
  2. ncbi Marfan-like skeletal phenotype in the tight skin (Tsk) mouse
    Tatjana Barisic-Dujmovic
    Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA
    Calcif Tissue Int 81:305-15. 2007
  3. ncbi Fibrillin-1 microfibril deposition is dependent on fibronectin assembly
    Rachel Kinsey
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Science, Michael Smith Building, Oxford Road, University of Manchester, Manchester M139PT, UK
    J Cell Sci 121:2696-704. 2008
  4. ncbi Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states
    Ronald D Cohn
    McKusick Nathans Institute of Genetic Medicine, Baltimore, Maryland 21205, USA
    Nat Med 13:204-10. 2007
  5. ncbi Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome
    Enid R Neptune
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nat Genet 33:407-11. 2003
  6. ncbi Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome
    Jennifer P Habashi
    Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Science 312:117-21. 2006
  7. ncbi ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation
    Ko Tsutsui
    Sekiguchi Biomatrix Signaling Project, Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Aichi Medical University, Nagakute, Aichi 480 1195, Japan
    J Biol Chem 285:4870-82. 2010
  8. ncbi Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome
    Daniel P Judge
    Division of Cardiology, Johns Hopkins University, Baltimore, Maryland 21205, USA
    J Clin Invest 114:172-81. 2004
  9. ncbi Enhanced expression of fibrillin-1, a constituent of the myocardial extracellular matrix in fibrosis
    Fatiha Bouzeghrane
    Institut de Recherches Cliniques de Montreal, Montreal, Quebec, Canada H2W 1R7
    Am J Physiol Heart Circ Physiol 289:H982-91. 2005
  10. ncbi A 16-month study of the development of genetic emphysema in tight-skin mice
    P A Martorana
    Department of Pharmacology, Cassella AG, Frankfurt Main, West Germany
    Am Rev Respir Dis 139:226-32. 1989

Research Grants

  1. Alveolization in Fibrillin-1 Defective Mice
    Enid Neptune; Fiscal Year: 2005
  2. The Role of Hepatocyte Growth Factor Signaling Airspace Homeostasis
    Enid Neptune; Fiscal Year: 2009
  3. 2005 Elastin and Elastic Fibers Gordon Conference
    CATHERINE KIELTY; Fiscal Year: 2005
  4. The Role of Hepatocyte Growth Factor Signaling Airspace Homeostasis
    Enid R Neptune; Fiscal Year: 2010
  5. Gene expression networks for metabolic syndrome traits in mice
    Thomas Drake; Fiscal Year: 2009
  6. Gene expression networks for metabolic syndrome traits in mice
    Thomas Drake; Fiscal Year: 2007
  7. Gene expression networks for metabolic syndrome traits in mice
    Thomas A Drake; Fiscal Year: 2010

Scientific Experts

Detail Information

Publications96

  1. ncbi B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis
    Minoru Hasegawa
    Department of Dermatology, Kanazawa University Graduate School of Medical Science, Japan
    Am J Pathol 169:954-66. 2006
    ..Thereby, B-cell depletion during disease onset suppressed skin fibrosis, indicating that B cells contribute to the initiation of systemic sclerosis pathogenesis in tight-skin mice but are not required for disease maintenance...
  2. ncbi Marfan-like skeletal phenotype in the tight skin (Tsk) mouse
    Tatjana Barisic-Dujmovic
    Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA
    Calcif Tissue Int 81:305-15. 2007
    ..dominant mutation located on mouse chromosome 2 and is associated with an intragenic duplication of the fibrillin 1 (Fbn1) gene...
  3. ncbi Fibrillin-1 microfibril deposition is dependent on fibronectin assembly
    Rachel Kinsey
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Science, Michael Smith Building, Oxford Road, University of Manchester, Manchester M139PT, UK
    J Cell Sci 121:2696-704. 2008
    ..Thus, pericellular microfibril assembly is regulated by fibronectin fibrillogenesis...
  4. ncbi Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states
    Ronald D Cohn
    McKusick Nathans Institute of Genetic Medicine, Baltimore, Maryland 21205, USA
    Nat Med 13:204-10. 2007
    ..Moreover, we show TGF-beta-induced failure of muscle regeneration and a similar therapeutic response in a dystrophin-deficient mouse model of Duchenne muscular dystrophy...
  5. ncbi Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome
    Enid R Neptune
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nat Genet 33:407-11. 2003
    ..These data indicate that matrix sequestration of cytokines is crucial to their regulated activation and signaling and that perturbation of this function can contribute to the pathogenesis of disease...
  6. ncbi Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome
    Jennifer P Habashi
    Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Science 312:117-21. 2006
    ....
  7. ncbi ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation
    Ko Tsutsui
    Sekiguchi Biomatrix Signaling Project, Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Aichi Medical University, Nagakute, Aichi 480 1195, Japan
    J Biol Chem 285:4870-82. 2010
    ..All together, these results indicated that ADAMTSL-6 is a novel microfibril-associated protein that binds directly to fibrillin-1 and promotes fibrillin-1 matrix assembly...
  8. ncbi Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome
    Daniel P Judge
    Division of Cardiology, Johns Hopkins University, Baltimore, Maryland 21205, USA
    J Clin Invest 114:172-81. 2004
    ..In keeping with this model, introduction of a WT FBN1 transgene on a heterozygous C1039G background rescues aortic phenotype...
  9. ncbi Enhanced expression of fibrillin-1, a constituent of the myocardial extracellular matrix in fibrosis
    Fatiha Bouzeghrane
    Institut de Recherches Cliniques de Montreal, Montreal, Quebec, Canada H2W 1R7
    Am J Physiol Heart Circ Physiol 289:H982-91. 2005
    ..In vitro and in vivo evidence suggests that ANG II can directly induce fibrillin-1 expression in cardiac fibroblasts. This protein can thus contribute to reactive and reparative processes...
  10. ncbi A 16-month study of the development of genetic emphysema in tight-skin mice
    P A Martorana
    Department of Pharmacology, Cassella AG, Frankfurt Main, West Germany
    Am Rev Respir Dis 139:226-32. 1989
    The tight-skin (tsk) mouse has been recently proposed as a model of genetically determined emphysema...
  11. ncbi Abnormal fibrillin-1 expression and chronic oxidative stress mediate endothelial mesenchymal transition in a murine model of systemic sclerosis
    Hao Xu
    Dept of Anesthesiology, Cardiovascular Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
    Am J Physiol Cell Physiol 300:C550-6. 2011
    ..The tight-skin (Tsk(-/+)) mouse is a model of SSc that displays many of the cellular features of the clinical disease...
  12. ncbi Microfibrils at basement membrane zones interact with perlecan via fibrillin-1
    Kerstin Tiedemann
    Department of Medical Molecular Biology, University of Lubeck, 23538 Lubeck, Germany
    J Biol Chem 280:11404-12. 2005
    ..The data presented indicate a functional significance for perlecan in anchoring microfibrils to basement membranes and in the biogenesis of microfibrils...
  13. ncbi TGF-beta-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome
    Connie M Ng
    McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    J Clin Invest 114:1586-92. 2004
    ....
  14. ncbi A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation
    L D Siracusa
    Department of Microbiology and Immunology, Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 5541, USA
    Genome Res 6:300-13. 1996
    ..The microfibrillar glycoprotein gene, fibrillin 1 (FBN1), on human chromosome 15q, provided a candidate for the Tsk mutation...
  15. ncbi Monocyte chemoattractant protein 3 as a mediator of fibrosis: Overexpression in systemic sclerosis and the type 1 tight-skin mouse
    Voon H Ong
    Royal Free Hospital and University College Medical School, London, UK
    Arthritis Rheum 48:1979-91. 2003
    ....
  16. ncbi Induction of skin fibrosis in mice expressing a mutated fibrillin-1 gene
    S Saito
    Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Mol Med 6:825-36. 2000
    b>Tight skin mice (TSK) bear a mutated Fibrillin-1 (Fbn-1) gene. Genetic studies show that the TSK mutation is closely associated with the Fbn-1 locus (0-0.7 cM)...
  17. ncbi Mutant fibrillin 1 from tight skin mice increases extracellular matrix incorporation of microfibril-associated glycoprotein 2 and type I collagen
    Raphael Lemaire
    Boston University School of Medicine, The Arthritis Center, Boston, Massachusetts 02118, USA
    Arthritis Rheum 50:915-26. 2004
    ..We also studied whether deposition of microfibril-associated glycoprotein 2 (MAGP-2), a protein that is associated with fibrillin 1, was altered in the skin of patients with SSc.
  18. ncbi Characterization of mutated protein encoded by partially duplicated fibrillin-1 gene in tight skin (TSK) mice
    S Saito
    Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Mol Immunol 36:169-76. 1999
    ..In addition, several microsatellite alleles near Fbn-1 gene were found associated with diffuse scleroderma. In TSK/+ mice, which develop a scleroderma-like syndrome, the Fbn-1 gene exhibits an inframe duplication of exons 17-40...
  19. ncbi Pathogenetic sequence for aneurysm revealed in mice underexpressing fibrillin-1
    L Pereira
    Brookdale Center for Developmental and Molecular Biology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Proc Natl Acad Sci U S A 96:3819-23. 1999
    ....
  20. ncbi Lack of endothelial cell apoptosis in the dermis of tight skin 1 and tight skin 2 mice
    R Sgonc
    University of Innsbruck, Austria
    Arthritis Rheum 42:581-4. 1999
  21. ncbi New insights into the assembly of extracellular microfibrils from the analysis of the fibrillin 1 mutation in the tight skin mouse
    B Gayraud
    Brookdale Center, Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York University, New York, New York 10029, USA
    J Cell Biol 150:667-80. 2000
    The Tight skin (Tsk) mutation is a duplication of the mouse fibrillin 1 (Fbn1) gene that results in a larger (418 kD) than normal (350 kD) protein; Tsk/+ mice display increased connective tissue, bone overgrowth, and lung emphysema...
  22. ncbi Regulation of limb patterning by extracellular microfibrils
    E Arteaga-Solis
    Brookdale Center, Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Cell Biol 154:275-81. 2001
    ..We also demonstrate that the Fbn2- null mutation is allelic to the recessive shaker-with-syndactyly (sy) locus on chromosome 18...
  23. ncbi The Tight skin mouse: demonstration of mutant fibrillin-1 production and assembly into abnormal microfibrils
    C M Kielty
    School of Biological Sciences, University of Manchester, Manchester, M13 9PT, United Kingdom
    J Cell Biol 140:1159-66. 1998
    Mice carrying the Tight skin (Tsk) mutation harbor a genomic duplication within the fibrillin-1 (Fbn 1) gene that results in a larger than normal in-frame Fbn 1 transcript...
  24. ncbi Fibrillins can co-assemble in fibrils, but fibrillin fibril composition displays cell-specific differences
    Noe L Charbonneau
    Department of Biochemistry and Molecular Biology, Shriners Hospital for Children, Oregon Health and Science University, Portland 97201, USA
    J Biol Chem 278:2740-9. 2003
    ..This surprising finding implicates distinct functions for fibrillin-2 in peripheral nerves, because a unique feature in humans and in mice mutant for fibrillin-2 is joint contractures that resolve over time...
  25. ncbi Endothelial dysfunction in murine model of systemic sclerosis: tight-skin mice 1
    I Marie
    Department of Zoology and Animal Biology, University of Geneva, Sciences III, 30 Quai Ernest Ansermet, 1211 Geneva 4, Switzerland
    J Invest Dermatol 119:1379-87. 2002
    ....
  26. ncbi Targetting of the gene encoding fibrillin-1 recapitulates the vascular aspect of Marfan syndrome
    L Pereira
    Brookdale Center for Developmental and Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nat Genet 17:218-22. 1997
    ....
  27. ncbi Hammerhead ribozyme-mediated silencing of the mutant fibrillin-1 of tight skin mouse: insight into the functional role of mutant fibrillin-1
    Rajesh P Menon
    Centre for Rheumatology, Royal Free and University College Medical School, Division of Medicine, University College London Hampstead Campus, Rowland Hill Street, London NW3 2PF2, UK
    Exp Cell Res 312:1463-74. 2006
    The tight skin (Tsk/+) mouse is a model for fibrotic disorders. The genetic defect in the Tsk/+ is an in-frame duplication between exons 17 and 40 of the fibrillin-1 gene which gives rise to a large transcript and protein...
  28. ncbi Emilin1 links TGF-beta maturation to blood pressure homeostasis
    Luca Zacchigna
    Developmental Signaling Laboratory, Department of Histology Microbiology and Medical Biotechnologies, University of Padua, viale Colombo 3, 35121 Padua, Italy
    Cell 124:929-42. 2006
    ..This study highlights the importance of modulation of TGF-beta availability in the pathogenesis of hypertension...
  29. ncbi Tight-skin, a new mutation of the mouse causing excessive growth of connective tissue and skeleton
    M C Green
    Am J Pathol 82:493-512. 1976
    A new dominant mutation, tight-skin (Tsk), is located on Chromosome 2, two recombination units distal to pallid (pa)...
  30. ncbi Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation
    Harikiran Nistala
    Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10021, USA
    J Cell Biol 190:1107-21. 2010
    ..Together, these findings identify the extracellular microfibrils as critical regulators of bone formation through the modulation of endogenous TGF-β and BMP signaling...
  31. ncbi In vivo studies of mutant fibrillin-1 microfibrils
    Noe L Charbonneau
    Shriners Hospital for Children, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Biol Chem 285:24943-55. 2010
    ..Taken together, these results suggest that perturbation of microfibril structure may underlie one of the major features of the Marfan syndrome: fragmentation of aortic elastic lamellae...
  32. ncbi Microfibril structure masks fibrillin-2 in postnatal tissues
    Noe L Charbonneau
    Shriners Hospital for Children, 3101 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    J Biol Chem 285:20242-51. 2010
    ..Furthermore, documentation of a novel cryptic site present in EGF4 in fibrillin-1 underscores the molecular complexity and tissue-specific differences in microfibril structure...
  33. ncbi Latent transforming growth factor beta-binding proteins and fibulins compete for fibrillin-1 and exhibit exquisite specificities in binding sites
    Robert N Ono
    Shriners Hospital for Children, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Biol Chem 284:16872-81. 2009
    ..These studies also suggest that the fibulins may affect matrix sequestration of LTBPs, because in vitro interactions between these proteins are competitive...
  34. ncbi p38 MAPK is an early determinant of promiscuous Smad2/3 signaling in the aortas of fibrillin-1 (Fbn1)-null mice
    Luca Carta
    Department of Pharmacology and Systems Therapeutics and the Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 284:5630-6. 2009
    ..Collectively, these findings indicate that improper activation of p38 MAPK is a precursor of constitutive Smad2/3 signaling in the aortic wall of a mouse model of neonatal lethal Marfan syndrome...
  35. ncbi Developmental expression of fibrillin genes suggests heterogeneity of extracellular microfibrils
    H Zhang
    Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York 10029, USA
    J Cell Biol 129:1165-76. 1995
    ..Accordingly, we propose that fibrillin-1 provides mostly force-bearing structural support, whereas fibrillin-2 predominantly regulates the early process of elastic fiber assembly...
  36. ncbi Intercellular adhesion molecule-1 deficiency attenuates the development of skin fibrosis in tight-skin mice
    Yukiyo Matsushita
    Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
    J Immunol 179:698-707. 2007
    The tight-skin (TSK/+) mouse, a genetic model for systemic sclerosis, develops cutaneous fibrosis. Although a fibrillin 1 gene mutation and immunological abnormalities have been demonstrated, the roles of adhesion molecules have not been ..
  37. ncbi TNF is a key mediator of septic encephalopathy acting through its receptor, TNF receptor-1
    Jessy J Alexander
    Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC5100, Chicago, IL 60637, USA
    Neurochem Int 52:447-56. 2008
    ....
  38. ncbi Increased collagen biosynthesis and increased expression of type I and type III procollagen genes in tight skin (TSK) mouse fibroblasts
    S A Jimenez
    J Biol Chem 261:657-62. 1986
    The Tight Skin (TSK) mouse is a mutant strain that displays connective tissue abnormalities characterized by excessive accumulation of collagen in skin, subcutaneous tissues, and some internal organs such as the heart...
  39. ncbi B-cell deficiency does not abrogate development of cutaneous hyperplasia in mice inheriting the defective fibrillin-1 gene
    K N Kasturi
    Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Autoimmun 10:505-17. 1997
    Tight-skin (TSK) mouse, the experimental model for scleroderma, develops cutaneous hyperplasia, cardiac hypertrophy, pulmonary emphysema and autoimmunity against scleroderma target autoantigens...
  40. ncbi Fibrillin genes map to regions of conserved mouse/human synteny on mouse chromosomes 2 and 18
    X Li
    Howard Hughes Medical Institute, Stanford University Medical Center, California 94305 5428
    Genomics 18:667-72. 1993
    ..In addition, the Fbn-1 gene maps in the vicinity of the gene for a connective tissue disorder on mouse chromosome 2 called Tight-skin (Tsk).
  41. ncbi Structure of the mutant fibrillin-1 gene in the tight skin (TSK) mouse
    C A Bona
    Department of Microbiology, Mount Sinai School of Medicine, New York, USA
    DNA Res 4:267-71. 1997
    Mice carrying the tight skin (TSK) mutation harbors a 3.0-kb genomic duplication (exons 17-40) of the fibrillin-1 gene (Fbn-1) located on band F of chromosome 2 as TSK mutation...
  42. ncbi Changes in fibrillin-1 in the endometrium during the early stages of pregnancy in mice
    Camila L Stumm
    Department of Cell and Developmental Biology, Laboratory of Biology of Reproduction and Extracellular Matrix, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
    Cells Tissues Organs 185:258-68. 2007
    ..Changes in the fibrillin-1 expression during the peri-implantation period suggest that fibrillin-1 plays a role in preparing the endometrium for embryo implantation...
  43. ncbi Fibrillins 1 and 2 perform partially overlapping functions during aortic development
    Luca Carta
    Laboratory of Genetics and Organogenesis, Hospital for Special Surgery, The Weill Medical College of Cornell University, New York, New York 10021, USA
    J Biol Chem 281:8016-23. 2006
    ....
  44. ncbi Fibrillln mutations in Marfan syndrome and related phenotypes
    F Ramirez
    Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029, USA
    Curr Opin Genet Dev 6:309-15. 1996
    A casual association has been established between mutations in the fibrillin 1 gene and Marfan syndrome and related phenotypes. Analysis of mutations in these disease types has provided new insights into microfibril assembly and function...
  45. ncbi Isoform-selective upregulation of mast cell chymase in the development of skin fibrosis in scleroderma model mice
    E Kakizoe
    Department of Pharmacology, Shimane Medical University, Izumo, Shimane, Japan
    J Invest Dermatol 116:118-23. 2001
    ..These results strongly support the contention that the connective-tissue-type mast cell chymase plays a crucial role in fibroproliferative remodeling of the skin...
  46. ncbi Noncanonical TGFβ signaling contributes to aortic aneurysm progression in Marfan syndrome mice
    Tammy M Holm
    Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Science 332:358-61. 2011
    ..Thus, noncanonical (Smad-independent) TGFβ signaling is a prominent driver of aortic disease in MFS mice, and inhibition of the ERK1/2 or JNK1 pathways is a potential therapeutic strategy for the disease...
  47. ncbi The Mohawk homeobox gene is a critical regulator of tendon differentiation
    Yoshiaki Ito
    Department of Systems Biomedicine, National Research Institute for Child Health and Development, Tokyo 157 8535, Japan
    Proc Natl Acad Sci U S A 107:10538-42. 2010
    ..These data indicate that Mkx plays a critical role in tendon differentiation by regulating type I collagen production in tendon cells...
  48. ncbi Targeted disruption of NeuroD, a proneural basic helix-loop-helix factor, impairs distal lung formation and neuroendocrine morphology in the neonatal lung
    Enid R Neptune
    Division of Pulmonary and Critical Care Medicine, Institute of Genetic Medicine, Howard Hughes Medical Institute, Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
    J Biol Chem 283:21160-9. 2008
    ..These results support an unanticipated role for NeuroD in the regulation of pulmonary neuroendocrine and alveolar morphogenesis and suggest an intimate connection between the neuroendocrine compartment and distal lung development...
  49. ncbi BAFF antagonist attenuates the development of skin fibrosis in tight-skin mice
    Takashi Matsushita
    Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
    J Invest Dermatol 127:2772-80. 2007
    The tight-skin (TSK/+) mouse, a genetic model for systemic sclerosis (SSc), develops cutaneous fibrosis and autoimmunity...
  50. ncbi Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism
    Jennifer P Habashi
    Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Science 332:361-5. 2011
    ..These data highlight the protective nature of AT2 signaling and potentially inform the choice of therapies in MFS and related disorders...
  51. ncbi Validation of nasal potential difference measurements in gut-corrected CF knockout mice
    Uta Griesenbach
    Department of Gene Therapy, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
    Am J Respir Cell Mol Biol 39:490-6. 2008
    ..These data should allow a more informed use of CF animals in future studies...
  52. ncbi Aortic wall mechanics and composition in a transgenic mouse model of Marfan syndrome
    V Marque
    Laboratoire de Pharmacologie Cardiovasculaire, Faculte de Pharmacie, Université Henri Poincaré Nancy, Nancy, France
    Arterioscler Thromb Vasc Biol 21:1184-9. 2001
    ..This result suggests that fragmentation of the medial elastic network and not a defect in early elastogenesis is 1 of the determinants of aortic dilatation in Marfan syndrome...
  53. ncbi Developmental expression of latent transforming growth factor beta binding protein 2 and its requirement early in mouse development
    J M Shipley
    Department of Medicine, Barnes Jewish Hospital at Washington University School of Medicine, St Louis, MO 63110, USA
    Mol Cell Biol 20:4879-87. 2000
    ....
  54. ncbi Tight-skin (Tsk) maps on mouse chromosome 2 within the region of linkage homology with human chromosome 15
    R C Doute
    DVA Medical Center, Newington, Connecticut 06111
    Genomics 22:223-5. 1994
    The tight-skin (Tsk) mutation has been mapped to mouse chromosome 2 between the visible markers pallid (pa) and agouti (a)...
  55. ncbi Molecular characterization of J558 genes encoding tight-skin mouse autoantibodies: identical heavy-chain variable genes code for antibodies with different specificities
    K N Kasturi
    Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029 6574
    Proc Natl Acad Sci U S A 91:8067-71. 1994
    ..Finally, in contrast to normal and other autoimmune mouse strains, the frequencies of D-D fusions and D inversions were higher in tight-skin mouse total immunoglobulin as well as autoantibody repertoires...
  56. ncbi The tight skin (Tsk) mutation in the mouse, a model for human fibrotic diseases, is tightly linked to the beta 2-microglobulin (B2m) gene on chromosome 2
    L D Siracusa
    Department of Microbiology and Immunology, Jefferson Cancer Institute, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 5541
    Genomics 17:748-51. 1993
    The Tsk mutation in the mouse is characterized by the excessive accumulation of collagen in skin and various internal organs, including the heart and lungs...
  57. ncbi Tight-skin mouse autoantibody repertoire: analysis of VH and VK gene usage
    K N Kasturi
    Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
    Mol Immunol 30:969-78. 1993
    In the previous studies we have shown that tight-skin (TSK) mouse is an experimental model for systemic sclerosis. This mutant mouse develops autoantibodies specific for scleroderma target antigens...
  58. ncbi The synthetic retinoid (4-hydroxyphenyl)retinamide decreases collagen expression in vitro and in the tight-skin mouse
    A M Delany
    Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755 3844
    Arthritis Rheum 36:983-93. 1993
    ..We documented the effect of the retinoid (4-hydroxyphenyl)retinamide on collagen expression in a tissue culture and in an animal model of scleroderma...
  59. ncbi A role for CD4+ T cells in the pathogenesis of skin fibrosis in tight skin mice
    V A Wallace
    Amgen Institute, Department of Immunology, University of Toronto, Ontario, Canada
    Eur J Immunol 24:1463-6. 1994
    The tight skin (Tsk/+) mouse represents a murine model of heritable fibrosis with some similarities to the skin fibrosis seen in human scleroderma. Tsk/+ animals display alterations in connective tissue in some internal organs...
  60. ncbi Hereditary emphysema in the tight-skin mouse. Evaluation of pathogenesis
    G A Rossi
    Am Rev Respir Dis 129:850-5. 1984
    The tight-skin (Tsk/+) mouse is a genetically determined model characterized by alveolar enlargement and physiologic evidence of emphysema...
  61. ncbi Partial cloning and sequencing of chick fibrillin-1 cDNA
    G Zhou
    Munroe Center for Human Genetics, University of Nebraska Medical Center, Omaha 68198 5430, USA
    In Vitro Cell Dev Biol Anim 36:19-25. 2000
    ..Antisense and sense riboprobes were synthesized and used in in situ hybridization in stage 14 chick embryos and high levels of FBN1 transcripts were observed in the heart...
  62. ncbi Apoptosis and proliferation of fibroblasts during postnatal skin development and scleroderma in the tight-skin mouse
    J L Pablos
    Servicio de Reumatologia, Hospital 12 de Octubre, Madrid, Spain
    J Histochem Cytochem 45:711-9. 1997
    Tight-skin (Tsk) is a dominant gene mutation that causes a fibrotic skin disease in mice, similar to human scleroderma...
  63. ncbi Urinary bladder function in the tight-skin mouse
    P A Longhurst
    Division of Urology, University of Pennsylvania School of Medicine, Philadelphia
    J Urol 148:1611-4. 1992
    ..It is suggested that other factors, such as the ratio of collagen subtypes or the collagen:elastin ratio may have more importance for the maintenance of bladder distension...
  64. ncbi Mast cells and their degranulation in the Tsk mouse model of scleroderma
    M Walker
    Proc Soc Exp Biol Med 180:323-8. 1985
    The Tsk mouse is a genetically transmitted example of cutaneous fibrosis which has been compared with human scleroderma...
  65. ncbi Loss of elastic fiber integrity and reduction of vascular smooth muscle contraction resulting from the upregulated activities of matrix metalloproteinase-2 and -9 in the thoracic aortic aneurysm in Marfan syndrome
    Ada W Y Chung
    Child and Family Research Institute, Department of Pediatrics, British Columbia Children s Hospital, University of British Columbia, Vancouver, British Columbia, Canada
    Circ Res 101:512-22. 2007
    ..The resulting elastic fiber degeneration with deterioration of the aortic contraction and mechanical properties may explain the pathogenesis of TAA...
  66. ncbi Neutrophil lysosomal dysfunctions in mutant C57 Bl/6J mice: interstrain variations in content of lysosomal elastase, cathepsin G and their inhibitors
    C Gardi
    Institute of General Pathology, University of Siena, Italy
    Biochem J 299:237-45. 1994
    ....
  67. ncbi Expression of a mutant human fibrillin allele upon a normal human or murine genetic background recapitulates a Marfan cellular phenotype
    Z A Eldadah
    Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
    J Clin Invest 95:874-80. 1995
    ..Lastly, this substantiation of a dominant-negative effect offers mutant allele knockout as a potential strategy for gene therapy...
  68. ncbi Prenatal lung epithelial cell-specific abrogation of Alk3-bone morphogenetic protein signaling causes neonatal respiratory distress by disrupting distal airway formation
    Jianping Sun
    Developmental Biology Program, Childrens Hospital Los Angeles, 4650 Sunset Blvd, MS 35, Los Angeles, CA 90027, USA
    Am J Pathol 172:571-82. 2008
    ..Therefore, our data suggest that deficiency of appropriate BMP signaling in lung epithelial cells results in prenatal lung malformation, neonatal atelectasis, and respiratory failure...
  69. ncbi Transforming growth factor-beta 1 and collagen gene expression during postnatal skin development and fibrosis in the tight-skin mouse
    J L Pablos
    Servicio de Reumatologia, Hospital 12 de Octubre, Madrid, Spain
    Lab Invest 72:670-8. 1995
    The tight-skin (Tsk) mutation in the mouse leads to widespread connective tissue abnormalities characterized by excessive collagen deposition that is similar to that observed in human scleroderma...
  70. ncbi Lung collagen synthesis and deposition in tight-skin mice with genetic emphysema
    C Gardi
    Institute of General Pathology, University of Siena, Italy
    Exp Mol Pathol 56:163-72. 1992
    The tight-skin (Tsk) mouse is a genetic model of pulmonary emphysema linked to a deficiency of serum antielastase. In this mouse occurrence of connective tissue abnormalities in various organs (systemic scleroderma) has been reported...
  71. ncbi A primary expression map of the chromosome 15q15 region containing the recessive form of limb-girdle muscular dystrophy (LGMD2A) gene
    N Chiannilkulchai
    Genethon, Evry, France
    Hum Mol Genet 4:717-25. 1995
    ..They were characterized for their sequences, physical positions within the YAC contig, and expression patterns. Among those specifically transcribed in muscle, the calpain gene is a good positional and functional candidate for LGMD2A...
  72. ncbi Granulated metrial gland cells in the pregnant uterus of mice expressing the collagen mutation tight-skin (Tsk/+)
    Y Kiso
    Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Canada
    Cell Tissue Res 268:393-6. 1992
    ..killer (NK)-like cell subset, were studied by histological examination of implantation sites in the mouse mutant Tsk/+. Tsk/+ mice overproduce collagens I and III...
  73. ncbi Complex integration of matrix, oxidative stress, and apoptosis in genetic emphysema
    Megan Podowski
    Divisionsof Pulmonary, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Am J Pathol 175:84-96. 2009
    ..We hypothesized that the tight-skin (TSK) mouse, which harbors a spontaneous internal duplication in the microfibrillar glycoprotein fibrillin-1, might show ..
  74. ncbi Experimental and bioinformatic characterisation of the promoter region of the Marfan syndrome gene, FBN1
    Kim M Summers
    The University of Edinburgh, The Roslin Institute and Royal Dick School of Veterinary Studies, Roslin, Midlothian EH25 9PS, UK
    Genomics 94:233-40. 2009
    ..Understanding the regulation of the FBN1 gene may lead to alternative therapeutic strategies for Marfan syndrome...
  75. ncbi Delayed-type hypersensitivity to elastase-soluble lung peptides in the tight-skin (Tsk) mouse
    F A DeLustro
    Cell Immunol 81:175-9. 1983
    ..of immunity to homologous connective tissue antigens was studied with respect to aging in the tight-skin (Tsk) mouse mutant...
  76. ncbi Nucleotide sequences of liver, lachrymal, and submaxillary gland mouse major urinary protein mRNAs: mosaic structure and construction of panels of gene-specific synthetic oligonucleotide probes
    K Shahan
    Mol Cell Biol 7:1938-46. 1987
    ..Shahan, M. Denaro, M. Gilmartin, Y. Shi, and E. Derman, Mol. Cell. Biol. 7:1947-1954, 1987), to characterize the expression of MUP genes I through V...
  77. ncbi The tight-skin mouse: an animal model of inherited emphysema
    G A Rossi
    Bull Eur Physiopathol Respir 16:157-66. 1980
  78. ncbi Are excessive granulation tissue formation and retarded wound contraction due to decreased collagenase activity in wounds in tight-skin mice?
    M S Agren
    Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, FL 33101
    Br J Dermatol 131:337-40. 1994
    ..Furthermore, this animal would model may prove useful in the understanding of the pathogenesis, and in exploration of treatment, of excessive granulation tissue formation during wound healing...
  79. ncbi Effect of targeted mutation in collagen V alpha 2 gene on development of cutaneous hyperplasia in tight skin mice
    R G Phelps
    Department of Pathology, Mount Sinai School of Medicine, New York, New York, USA
    Mol Med 4:356-60. 1998
    ..exhibits skeletal abnormalities, skin fragility, and alterations in the collagen fiber organization, whereas the TSK/+ mouse, which is defective in fibrillin-1, the major component of microfibrils present in the extracellular matrix,..
  80. ncbi Distribution of fibronectin, type I collagen, type IV collagen, and laminin in the cardiac jelly of the mouse embryonic heart with retinoic acid-induced complete transposition of the great arteries
    Y Nakajima
    Department of Anatomy, Saitama Medical School, Japan
    Anat Rec 249:478-85. 1997
    ..During cushion tissue formation, basement membrane antigens play an important role in the regulation of this endothelial-mesenchymal transformation...
  81. ncbi Silicone does not potentiate development of the scleroderma-like syndrome in tight skin (TSK/+) mice
    C Frondoza
    Johns Hopkins Dept of Molecular Microbiology and Immunology, Baltimore, Maryland 21239, USA
    J Autoimmun 9:473-83. 1996
    ..The purpose of the present study was to determine the effect of silicone on the tight skin (TSK/+) mouse which develops a scleroderma-like syndrome and on its normal pa/pa TSK/- littermate...
  82. ncbi A role for T helper 2 cells in mediating skin fibrosis in tight-skin mice
    C J Ong
    Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada
    Cell Immunol 196:60-8. 1999
    Mice heterozygous for the tight-skin (Tsk) mutation develop skin fibrosis. Previous studies have implicated a role for the immune system and, specifically, CD4(+) T cells, in the etiology of skin fibrosis in Tsk/+ mice...
  83. ncbi Corn1: a mouse model for corneal surface disease and neovascularization
    R S Smith
    Jackson Laboratory, Bar Harbor, Maine 04609 1500, USA
    Invest Ophthalmol Vis Sci 37:397-404. 1996
    ..To describe a new mouse model of corneal surface disease and neovascularization...
  84. ncbi B Lymphocyte signaling established by the CD19/CD22 loop regulates autoimmunity in the tight-skin mouse
    Noriko Asano
    Department of Regenerative Medicine, Research Institute, International Medical Center of Japan, Tokyo, Japan
    Am J Pathol 165:641-50. 2004
    ..CD19 deficiency in B cells also attenuates skin fibrosis in the tight-skin (TSK/+) mouse, a genetic model for SSc. Herein we analyzed two transgenic mouse lines that overexpress CD19...
  85. ncbi Immunological characterization of (tight skin/NZB)F1 hybrid mice with connective tissue and autoimmune features resembling human systemic sclerosis
    M H Bocchieri
    Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107
    J Autoimmun 6:337-51. 1993
    A new murine model of Systemic Sclerosis (SSc) has been developed by breeding the Tsk+/+pa tight skin mouse (TSK) and the autoimmune disease-prone NZB strain to produce an F1 hybrid displaying the connective tissue abnormalities of the ..
  86. ncbi The mouse tight skin (Tsk) phenotype is not dependent on the presence of mature T and B lymphocytes
    L D Siracusa
    Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107-5541, USA
    Mamm Genome 9:907-9. 1998
  87. ncbi Mast cell accumulation and cytokine expression in the tight skin mouse model of scleroderma
    Hong Wei Wang
    School of Medical Sciences, The University of New South Wales, Sydney, Australia
    Exp Dermatol 14:295-302. 2005
    The tight skin (Tsk) mouse develops many pathological changes seen in human scleroderma, such as increased collagen content and mast cell density...
  88. ncbi Increased collagen synthesis and increased content of type VI collagen in myocardium of tight skin mice
    R I Bashey
    Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107
    Cardiovasc Res 27:1061-5. 1993
    The tight skin mouse (TSK) is a mutant strain characterised by excessive collagen accumulation in skin and some internal organs such as the heart...
  89. ncbi Endothelial dysfunction and compromised eNOS/Akt signaling in the thoracic aorta during the progression of Marfan syndrome
    A W Y Chung
    Child and Family Research Institute and Departments of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada
    Br J Pharmacol 150:1075-83. 2007
    ..We hypothesized that MFS impaired endothelial function and nitric oxide (NO) production in the aorta...
  90. ncbi Cardiac collagen changes during the development of right ventricular hypertrophy in tight-skin mice with emphysema
    C Gardi
    Institute of General Pathology, University of Siena, Italy
    Exp Mol Pathol 60:100-7. 1994
    The tight-skin (Tsk) mouse is a genetic model of pulmonary emphysema. In this mouse, right ventricular hypertrophy (RVH) starts to develop at approximately 8 months of age, probably as a consequence of the emphysema...
  91. ncbi The tight-skin (Tsk) mutation is closely linked to B2m on mouse chromosome 2
    E T Everett
    Department of Medicine, Medical University of South Carolina, Charleston 29425-2229
    Mamm Genome 5:55-7. 1994
  92. ncbi Immunochemical and molecular characterization of anti-RNA polymerase I autoantibodies produced by tight skin mouse
    S Shibata
    Department of Microbiology, Mount Sinai School of Medicine, New York 10029 6574
    J Clin Invest 92:984-92. 1993
    ..Previous investigations have shown that the tight skin (TSK) mouse is an experimental model for systemic sclerosis...
  93. ncbi The role of mast cells in the development of skin fibrosis in tight-skin mutant mice
    E T Everett
    Department of Medicine, Medical University of South Carolina, Charleston 29425 2229
    Comp Biochem Physiol A Physiol 110:159-65. 1995
    ..The tight-skin (Tsk) mouse develops an inherited fibrotic disease (sharing many similarities with the human disease scleroderma, ..
  94. ncbi Molecular characterization of a serine/threonine kinase in the DiGeorge minimal critical region
    E Goldmuntz
    The Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, The Department of Pediatrics, 19104, USA
    Gene 198:379-86. 1997
    ..Based on its position in the MDGCR and possible function, the gene reported here is a candidate for the features seen in the 22q11 deletion syndrome...
  95. ncbi Induction of skin fibrosis and autoantibodies by infusion of immunocompetent cells from tight skin mice into C57BL/6 Pa/Pa mice
    R G Phelps
    Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029 6574
    J Autoimmun 6:701-18. 1993
    b>Tight skin (TSK/+) mice develop a cutaneous hyperplasia associated with the occurrence of autoantibodies characteristic for scleroderma...
  96. ncbi A scanning electron microscopic investigation of genetic emphysema in tight-skin, pallid, and beige mice, three different C57 BL/6J mutants
    M Keil
    Hoechst AG, Pharma Development Pathology, Frankfurt Main, Germany
    Lab Invest 74:353-62. 1996
    Three mutants of the C57 BL/6J strain, i.e., the tight-skin (Tsk), pallid (pa), and beige (bg) mice have been reported to develop spontaneous emphysema...

Research Grants13

  1. Alveolization in Fibrillin-1 Defective Mice
    Enid Neptune; Fiscal Year: 2005
    ..abstract_text> ..
  2. The Role of Hepatocyte Growth Factor Signaling Airspace Homeostasis
    Enid Neptune; Fiscal Year: 2009
    ..Specific Aim 1, we target gain of HGF function with a detailed dose-response analysis of HGF supplementation in the TSK model of emphysema...
  3. 2005 Elastin and Elastic Fibers Gordon Conference
    CATHERINE KIELTY; Fiscal Year: 2005
    ..As in past years, these personal interactions will result in new collaborative studies and stimulate novel avenues of elastic fiber investigation. ..
  4. The Role of Hepatocyte Growth Factor Signaling Airspace Homeostasis
    Enid R Neptune; Fiscal Year: 2010
    ..Specific Aim 1, we target gain of HGF function with a detailed dose-response analysis of HGF supplementation in the TSK model of emphysema...
  5. Gene expression networks for metabolic syndrome traits in mice
    Thomas Drake; Fiscal Year: 2009
    ....
  6. Gene expression networks for metabolic syndrome traits in mice
    Thomas Drake; Fiscal Year: 2007
    ....
  7. Gene expression networks for metabolic syndrome traits in mice
    Thomas A Drake; Fiscal Year: 2010
    ....