Research Topics
Genomes and Genes
| C D FunkSummaryAffiliation: University of Pennsylvania Country: USA Publications
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Detail Information
Publications
Lipoxygenase genes and their targeted disruptionColin D Funk
Department of Pharmacology, Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia 19104, USA
Prostaglandins Other Lipid Mediat 68:303-12. 2002..While the knockout mice appear outwardly normal, a number of important findings have been discovered using these mice and these will be covered in this review...- Prostaglandins and leukotrienes: advances in eicosanoid biologyC D Funk
Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA
Science 294:1871-5. 2001..Important insights into the mechanisms of inflammatory responses, pain, and fever have been gleaned from our current understanding of eicosanoid biology... - 12/15-lipoxygenase, oxidative modification of LDL and atherogenesisC D Funk
BRBII III Rm 814, Department of Pharmacology, Center for Experimental Therapeutics, University of Pennsylvania, 421 Curie Blvd, Philadelphia, PA 19104 6160, USA
Trends Cardiovasc Med 11:116-24. 2001..In contrast, previous experiments with macrophage expressing 15-lipoxygenase transgenic rabbits have suggested an anti-atherogenic role. Possible explanations are presented that may elucidate these differences... - Absence of 12/15-lipoxygenase expression decreases lipid peroxidation and atherogenesis in apolipoprotein e-deficient miceT Cyrus
Center for Experimental Therapeutics, Department of Medicine, University of Pennsylvania, Philadelphia, USA
Circulation 103:2277-82. 2001.... - The murine cysteinyl leukotriene 2 (CysLT2) receptor. cDNA and genomic cloning, alternative splicing, and in vitro characterizationY Hui
Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA
J Biol Chem 276:47489-95. 2001..The identification of mCysLT(2)R will be useful for establishing CysLT(2)R-deficient mice and determining novel leukotriene functions... - Cloning of a human "epidermal-type" 12-lipoxygenase-related gene and chromosomal localization to 17p13D Sun
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia PA USA
Cytogenet Cell Genet 81:79-82. 1998..Based on several criteria, humans appear to lack a functional e-12LO gene but instead have acquired an expressed pseudogene. The pseudogene designated ALOX12P2 was localized to chromosome 17p13 by analysis of somatic hybrid DNA panels... - Disruption of 12/15-lipoxygenase expression in peritoneal macrophages. Enhanced utilization of the 5-lipoxygenase pathway and diminished oxidation of low density lipoproteinD Sun
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6100, USA
J Biol Chem 271:24055-62. 1996..Thus, 12/15-lipoxygenase-deficient mice will be useful for the study of interaction between lipoxygenase pathways and determination of the in vivo role of 12/15-lipoxygenase-catalyzed oxidation of LDL in atherogenesis... - Molecular cloning and functional characterization of murine cysteinyl-leukotriene 1 (CysLT(1)) receptorsV Martin
Center for Experimental Therapeutics, 814 BRB II III, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104 6160, USA
Biochem Pharmacol 62:1193-200. 2001..Functional elucidation of mCysLT(1)R properties as described here will enable further experiments to clarify the selective role of LTD(4) in murine models of inflammation and asthma... 
Disruption of the 12/15-lipoxygenase gene diminishes atherosclerosis in apo E-deficient miceT Cyrus
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Clin Invest 103:1597-604. 1999..The combined data indicate a role for 12/15-lipoxygenase in the pathogenesis of atherosclerosis and suggest that inhibition of this enzyme may decrease disease progression...- Human 12(R)-lipoxygenase and the mouse ortholog. Molecular cloning, expression, and gene chromosomal assignmentD Sun
Center for Experimental Therapeutics, Departments of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 273:33540-7. 1998..5 in epidermis, nasal epithelium, and surface of the tongue. These results broaden the mammalian lipoxygenase family to include a 12(R)-lipoxygenase whose biological function remains to be determined... - Insight into prostaglandin, leukotriene, and other eicosanoid functions using mice with targeted gene disruptionsS C Austin
Center for Experimental Therapeutics, Stellar Chance Labs, University of Pennsylvania, Philadelphia 19104, USA
Prostaglandins Other Lipid Mediat 58:231-52. 1999..g., receptors for various prostaglandins). This minireview will outline the phenotype of these knockout mice and what has been learned about eicosanoid functions through use of this novel methodology... - Absence of 12/15 lipoxygenase reduces brain oxidative stress in apolipoprotein E-deficient miceCinzia M Chinnici
Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, John Morgan Building, Room 124, Philadelphia, PA 19104, USA
Am J Pathol 167:1371-7. 2005.... - Role of 'platelet-type' 12-lipoxygenase in skin carcinogenesisJ Virmani
Department of Pharmacology, Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, PA 19104-6160, USA
Cancer Lett 162:161-5. 2001..Overall, these data suggest that the P-12LO pathway may contribute to tumor incidence and progression in two-stage, but not complete, carcinogenesis, depending on the genetic background... - The N-terminal "beta-barrel" domain of 5-lipoxygenase is essential for nuclear membrane translocationX S Chen
Department of Pharmacology, Center for Experimental Therapeutics University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 276:811-8. 2001..Thus, the predicted beta-barrel domain of 5-lipoxygenase may function like the C2 domain within protein kinase C and cytosolic phospholipase A(2) with unique determinants that direct its localization to the nuclear envelope... - Increased platelet sensitivity to ADP in mice lacking platelet-type 12-lipoxygenaseE N Johnson
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Proc Natl Acad Sci U S A 95:3100-5. 1998..The enhanced ADP sensitivity of P-12LO-/- mice appears to reveal a mechanism by which a product of the P-12LO pathway suppresses platelet activation by ADP... - The molecular biology of mammalian lipoxygenases and the quest for eicosanoid functions using lipoxygenase-deficient miceC D Funk
Stellar-Chance Laboratories, University of Pennsylvania, Philadelphia 19104-6100, USA
Biochim Biophys Acta 1304:65-84. 1996 - Basal transepidermal water loss is increased in platelet-type 12-lipoxygenase deficient miceE N Johnson
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
J Invest Dermatol 112:861-5. 1999..These results indicate that the platelet-type 12-lipoxygenase pathway in mice is partly responsible for normal permeability barrier function but the mechanism awaits further elucidation... - 12/15-lipoxygenase is increased in Alzheimer's disease: possible involvement in brain oxidative stressDomenico Pratico
Center for Experimental Therapeutics, Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Am J Pathol 164:1655-62. 2004..These data show that the 12/15-LOX metabolic pathway is increased and correlates with an oxidative imbalance in the AD brain, implying that this enzyme might contribute to the pathogenesis of this neurodegenerative disorder... - 12/15-Lipoxygenase gene disruption and vitamin E administration diminish atherosclerosis and oxidative stress in apolipoprotein E deficient mice through a final common pathwayLei Zhao
Institute of Translational Medicine and Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA
Prostaglandins Other Lipid Mediat 78:185-93. 2005..These results suggest that early 12/15-LO-mediated lipid peroxidation triggers ensuing non-enzymatic peroxidation that is susceptible to Vitamin E antioxidant action in a common pathway of atherogenesis... - Selective interleukin-12 synthesis defect in 12/15-lipoxygenase-deficient macrophages associated with reduced atherosclerosis in a mouse model of familial hypercholesterolemiaLei Zhao
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 277:35350-6. 2002..The data provide support for a novel mechanism linking the 12/15-lipoxygenase pathway to a known immunomodulatory Th1 cytokine in atherogenesis... - Augmented responses to morphine and cocaine in mice with a 12-lipoxygenase gene disruptionCarrie L Walters
Department of Pharmacology, 125 John Morgan Building, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, PA 19104 6084, USA
Psychopharmacology (Berl) 170:124-31. 2003..A similar mechanism has been shown for the regulation of glutamate release in the ventral tegmental area (VTA) during acute withdrawal from morphine, although the functional significance of these effects in vivo are not known... - 12-lipoxygenase metabolites of arachidonic acid mediate metabotropic glutamate receptor-dependent long-term depression at hippocampal CA3-CA1 synapsesSteven J Feinmark
Department of Pharmacology, Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA
J Neurosci 23:11427-35. 2003.... - Role of decay-accelerating factor in regulating complement activation on the erythrocyte surface as revealed by gene targetingX Sun
Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 96:628-33. 1999.... - Functional expression and cellular localization of a mouse epidermal lipoxygenaseC D Funk
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, USA
J Biol Chem 271:23338-44. 1996..The epidermal lipoxygenase gene (Aloxe) resides on mouse chromosome 11 closely linked with the two 12-lipoxygenase genes (Alox12p and Alox12l)... - Leukotriene binding, signaling, and analysis of HIV coreceptor function in mouse and human leukotriene B4 receptor-transfected cellsV Martin
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 274:8597-603. 1999..Isolation of the m-BLTR gene will form the basis of future experiments to elucidate the selective role of LTB4, as opposed to cysteinyl-leukotrienes, in murine models of inflammation... - Cyclooxygenase-2-dependent prostacyclin formation and blood pressure homeostasis: targeted exchange of cyclooxygenase isoforms in miceYing Yu
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 153 Johnson Pavilion, Philadelphia, PA 19104, USA
Circ Res 106:337-45. 2010..Both traditional nonsteroidal antiinflammatory drugs (NSAIDs) that inhibit COX-1 and COX-2 and NSAIDs designed to be selective for inhibition of COX-2 cause sodium retention and elevate blood pressure... - Leukotriene-deficient mice generated by targeted disruption of the 5-lipoxygenase geneC D Funk
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
Adv Prostaglandin Thromboxane Leukot Res 23:145-50. 1995 - The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysmLei Zhao
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, USA
Nat Med 10:966-73. 2004..These data link the 5-LO pathway to hyperlipidemia-dependent inflammation of the arterial wall and to pathogenesis of aortic aneurysms through a potential chemokine intermediary route... - Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular functionYan Cheng
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Clin Invest 116:1391-9. 2006..These results suggest that inhibitors of mPGES-1 may retain their antiinflammatory efficacy by depressing PGE(2), while avoiding the adverse cardiovascular consequences associated with PGHS-2-mediated PGI(2) suppression... - Genetic model of selective COX2 inhibition reveals novel heterodimer signalingYing Yu
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 421 Curie Boulevard, BRB II III, Philadelphia, Pennsylvania 19104, USA
Nat Med 12:699-704. 2006..The heterodimerization of PGHS1-PGHS2 may explain how the ductus arteriosus closes normally at birth in mice expressing PGHS2 Y385F, but not in PGHS2-null mice... - Characterization of epidermal 12(S) and 12(R) lipoxygenasesMaeve McDonnell
Center for Experimental Therapeutics, Rm 820 BRB II/III, University of Pennsylvania, Philadelphia, PA 19104, USA
Adv Exp Med Biol 507:147-53. 2002 - Effect of low-dose aspirin on vascular inflammation, plaque stability, and atherogenesis in low-density lipoprotein receptor-deficient miceTillmann Cyrus
Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA
Circulation 106:1282-7. 2002..We conclude that low-dose aspirin might be rationally evaluated in the progression and evolution of human atherosclerotic plaque... - A novel genetic model of selective COX-2 inhibition: comparison with COX-2 null miceYing Yu
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
Prostaglandins Other Lipid Mediat 82:77-84. 2007..In this short review, we compare a novel genetic COX-2 selective inhibition mouse model with the originally described COX-2 null mice in these different physiological functions... - Differential impact of prostaglandin H synthase 1 knockdown on platelets and parturitionYing Yu
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
J Clin Invest 115:986-95. 2005..PGHS1(Neo/Neo) mice provide a model of low-dose aspirin therapy that elucidates how prevention or delay of preeclampsia might be achieved without compromising reproductive function... - Targeted cyclooxygenase gene (ptgs) exchange reveals discriminant isoform functionalityYing Yu
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 282:1498-506. 2007..These mice will provide a valuable reagent with which to elucidate the distinct roles of the COX enzymes in mammalian biology... - Lipoxygenase pathways in atherogenesisLei Zhao
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, USA
Trends Cardiovasc Med 14:191-5. 2004..Development of novel pharmacologic tools to dissect the individual enzymes and receptors in the LO pathways should improve understanding of the individual components in the inflammatory aspects of atherosclerosis disease progression... - Angiotensin II-induced abdominal aortic aneurysm occurs independently of the 5-lipoxygenase pathway in apolipoprotein E-deficient miceRichard Yang Cao
Department of Physiology, Queen s University, Kingston, Ont K7L 3N6, Canada
Prostaglandins Other Lipid Mediat 84:34-42. 2007..Abrogation of the 5-LO pathway in mice indicates a lack of role of leukotrienes in Ang II-induced AAA pathogenesis stressing the need for additional non-rodent AAA pre-clinical models to be tested... - The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient miceMichael P W Moos
The Institute for Vascular Medicine, Friedrich Schiller University of Jena, Germany
Arterioscler Thromb Vasc Biol 25:2386-91. 2005..Cells of adaptive immunity have been implicated in atherogenesis. Though substantial information is available on immune cells in atherosclerotic lesions of the lamina intima, cells in the lamina adventitia have received less attention... - Actin polymerization in macrophages in response to oxidized LDL and apoptotic cells: role of 12/15-lipoxygenase and phosphoinositide 3-kinaseYury I Miller
Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
Mol Biol Cell 14:4196-206. 2003.... - Elevated endothelial nitric oxide bioactivity and resistance to angiotensin-dependent hypertension in 12/15-lipoxygenase knockout micePeter B Anning
Department of Medical Biochemistry and Immunology, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK
Am J Pathol 166:653-62. 2005.... - Critical role of macrophage 12/15-lipoxygenase for atherosclerosis in apolipoprotein E-deficient miceYuqing Huo
University of Virginia, Charlottesville, VA, USA
Circulation 110:2024-31. 2004..12/15-LO is expressed in a variety of cells, including vascular cells, adipocytes, macrophages, and cardiomyocytes. The purpose of this study was to determine which cellular source of 12/15-LO is important for atherosclerosis... - Anion exchanger 2 is essential for spermiogenesis in miceJuan F Medina
Division of Hepatology and Gene Therapy, University Hospital School of Medicine, Fundacion para la Investigacion Medica Aplicada, University of Navarra, E 31008 Pamplona, Spain
Proc Natl Acad Sci U S A 100:15847-52. 2003..Our findings reveal an essential role of Ae2 in mouse spermiogenesis and stress the recently postulated involvement of bicarbonate in germ-cell differentiation through the bicarbonate-sensitive soluble-adenylyl-cyclase pathway... - Endothelial cysteinyl leukotriene 2 receptor expression mediates myocardial ischemia-reperfusion injuryWei Jiang
Department of Physiology, 433 Botterell Hall, Stuart St, Queen s University, Kingston, ON K7L 3N6 Canada
Am J Pathol 172:592-602. 2008.... - Selective 5-lipoxygenase expression in Langerhans cells and impaired dendritic cell migration in 5-LO-deficient mice reveal leukotriene action in skinSandra Doepping
Institute for Vascular Medicine, Friedrich Schiller University of Jena, Jena, Germany
J Invest Dermatol 127:1692-700. 2007.... - Is there a role for the macrophage 5-lipoxygenase pathway in aortic aneurysm development in apolipoprotein E-deficient mice?Colin D Funk
Department of Physiology, Queen s University, Kingston, ON K7L 3N6 Canada
Ann N Y Acad Sci 1085:151-60. 2006..We are currently exploring the potential mechanisms for 5-LO/LT involvement in aneurysm pathogenesis and if this pathway might come into play in other models such as induction by angiotensin II... - Identification of 5-lipoxygenase as a major gene contributing to atherosclerosis susceptibility in miceMargarete Mehrabian
Department of Medicine, UCLA School of Medicine, Los Angeles, Calif 90095 1679, USA
Circ Res 91:120-6. 2002..These results indicate that 5-LO contributes importantly to the atherogenic process and they provide strong presumptive evidence that reduced 5-LO expression is partly responsible for the resistance to atherosclerosis in CON6 mice... - Elevated expression of 12/15-lipoxygenase and cyclooxygenase-2 in a transgenic mouse model of prostate carcinomaScott B Shappell
Department of Pathology, Vanderbilt Prostate Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232 2561, USA
Cancer Res 63:2256-67. 2003.... - Lipoxygenase pathways as mediators of early inflammatory events in atherosclerosisColin D Funk
Arterioscler Thromb Vasc Biol 26:1204-6. 2006 - Macrophage-specific expression of group IIA sPLA2 results in accelerated atherogenesis by increasing oxidative stressUwe J F Tietge
Department of Medicine, Charite Campus Mitte, Humboldt University, Berlin, Germany
J Lipid Res 46:1604-14. 2005....