Impact of chromosome 2 obesity loci on cardiovascular complications of insulin
resistance in LDL receptor-deficient C57BL/6 mice.
Authors Estrada-Smith D, Collins AR, Wang X, Crockett C, Castellani L, Lusis AJ, Davis
RC
Submitted By Richard Davis on 2/11/2009
Status Published
Journal Diabetes
Year 2006
Date Published 8/1/2006
Volume : Pages 55(8) : 2265 - 2271
PubMed Reference 16873689
Abstract Previous characterization of mouse chromosome 2 identified genomic intervals
that influence obesity, insulin resistance, and dyslipidemia. For this,
resistant CAST/Ei (CAST) alleles were introgressed onto a susceptible C57BL/6J
background to generate congenic strains with CAST alleles encompassing 67-162 Mb
(multigenic obesity 6 [MOB6]) and 84-180 Mb (MOB5) from mouse chromosome 2. To
examine the effects of each congenic locus on atherosclerosis and glucose
disposal, we bred each strain onto a sensitizing LDL receptor-null (LDLR(-/-))
C57BL/6J background to predispose them to hypercholesterolemia and insulin
resistance. LDLR(-/-) congenics and controls were characterized for measures of
atherogenesis, insulin sensitivity, and obesity. We identified a genomic
interval unique to the MOB6 congenic (72-84 Mb) that dramatically decreased
atherosclerosis by approximately threefold and decreased insulin resistance.
This region also reduced adiposity twofold. Conversely, the congenic region
unique to MOB5 (162-180 Mb) increased insulin resistance but had little effect
on atherosclerosis and adiposity. The MOB congenic intervals are concordant to
human and rat quantitative trait loci influencing diabetes and atherosclerosis
traits. Thus, our results define a strategy for studying the poorly understood
interactions between diabetes and atherosclerosis and for identifying genes
underlying the cardiovascular complications of insulin resistance.


Investigators with authorship
NameInstitution
Richard DavisUniversity of California Los Angeles

Complications









Genes
SymbolDescription
Mob6multigenic obesity 6
Mob5multigenic obesity 5