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Characterization of 5LO transgenic mouse model for atherosclerosis, adipocity, and diabetes related traits
Author(s) -
Nebohacova Martina,
Zhou Zhiqiang,
Fielder Thomas,
Lusis Aldons J.,
Mehrabian Margarete
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a485-a
Subject(s) - transgene , genetically modified mouse , diabetes mellitus , biology , phenotype , arachidonic acid , inflammation , medicine , endocrinology , gene , enzyme , genetics , biochemistry
5‐lipoxygenase (5LO) is the key enzyme in leukotriene biosynthesis, catalyzing the initial steps in the conversion of arachidonic acid to these biologically active lipid mediators. Based on genetic and metabolic studies, there is evidence for the involvement of 5LO in several chronic pathologies, including those associated with CHD, adipocity, and diabetes related traits in both mice and humans. We have previously found that null mutation of the gene significantly decreases aortic lesion formation when on a C57BL/6J (B6) or a hyperlipidemic (apoE, LDLR KOs) background. We have also shown that decreased 5LO expression is associated with adipocity, increased leptin expression, and impaired insulin secretion. We have now introduced additional copies of the endogenous C57BL/6J 5LO gene into the genome of C57BL/6J mouse strain. We now have 5LO transgenics with copy numbers ranging from 2 to 10. The transgenes bred either onto a B6 background and apoE−/ − hyperlipidemic background (5LOtg/apoE) have allowed us to better characterize the functional roles of 5LO in vascular inflammation, adipocity and diabetes related traits, beta‐cell function particularly.