Premium
Rat models for the study of cholesterol disequilibria
Author(s) -
McCoy Aaron Michael
Publication year - 2012
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.26.1_supplement.lb417
Subject(s) - medicine , endocrinology , triglyceride , cholesterol , apolipoprotein e , obesity , diabetes mellitus , homeostasis , ldl receptor , biology , glucose homeostasis , body weight , chemistry , disease , lipoprotein , insulin resistance
Cholesterol homeostasis has been correlated to several human disease pathologies including obesity, diabetes, atherosclerosis, Alzheimer's disease and Huntington's disease. To develop a better understanding of the mechanisms of cholesterol regulation we have created rats with manipulations in the genes Apoe, Ldlr and Lep. These mutants were created by injection of zinc finger nucleases (ZFN) into one‐cell Sprague‐Dawley rat embryos. Apoe KO animals demonstrate a 4.5 fold increase in total serum cholesterol concentration at 10 weeks relative to their wild type littermates. Rats deficient in Ldlr demonstrate a 4–8 fold increase in total serum cholesterol and a slight increase (~10%) in weight gain at 18 weeks relative to WT. Lep deficient rats demonstrate a 2 fold increase in body weight at 18 weeks relative to WT and a nearly a 4‐fold increase total triglyceride blood concentrations post 16hr fast. Additionally, we performed a glucose tolerance assay in Lep deficient and WT animals at 5 and 10 week time points. Lep deficient animals consistently demonstrated increased concentrations of glucose in the blood, indicating impaired glucose tolerance in the absence of functional Lep.