title: Genetic determinants of atherosclerosis, obesity, and energy balance in consomic mice.
abstract: Metabolic diseases such as obesity and atherosclerosis result from complex interactions between environmental factors and genetic variants. A panel of chromosome substitution strains (CSSs) was developed to characterize genetic and dietary factors contributing to metabolic diseases and other biological traits and biomedical conditions. Our goal here was to identify quantitative trait loci (QTLs) contributing to obesity, energy expenditure, and atherosclerosis. Parental strains C57BL/6 and A/J together with a panel of 21 CSSs derived from these progenitors were subjected to chronic feeding of rodent chow and atherosclerotic (females) or diabetogenic (males) test diets, and evaluated for a variety of metabolic phenotypes including several traits unique to this report, namely fat pad weights, energy balance, and atherosclerosis. A total of 297 QTLs across 35 traits were discovered, two of which provided significant protection from atherosclerosis, and several dozen QTLs modulated body weight, body composition, and circulating lipid levels in females and males. While several QTLs confirmed previous reports, most QTLs were novel. Finally, we applied the CSS quantitative genetic approach to energy balance, and identified three novel QTLs controlling energy expenditure and one QTL modulating food intake. Overall, we identified many new QTLs and phenotyped several novel traits in this mouse model of diet-induced metabolic diseases.
authors.affiliation: Institute for Systems Biology, 401 North Terry Ave, Seattle, WA, 98109, USA.
authors.forename: Sabrina H
authors.initials: SH
authors.lastname: Spiezio
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Amon
authors.forename: Timothy S
authors.initials: TS
authors.lastname: McMillen
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Vick
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Houston
authors.forename: Mark
authors.initials: M
authors.lastname: Caldwell
authors.forename: Kayoko
authors.initials: K
authors.lastname: Ogimoto
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Morton
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kirk
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schwartz
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Nadeau
authors.forename: Renée C
authors.initials: RC
authors.lastname: LeBoeuf
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics*; D001823:Body Composition; D001835:Body Weight; D033481:Chromosomes, Mammalian / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D040641:Quantitative Trait Loci