Atherosclerosis quantitative trait loci are sex- and lineage-dependent in an
intercross of C57BL/6 and FVB/N low-density lipoprotein receptor-/- mice.
Authors Teupser D, Tan M, Persky AD, Breslow JL
Submitted By Jan Breslow on 2/23/2009
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2006
Date Published 1/3/2006
Volume : Pages 103(1) : 123 - 128
PubMed Reference 16380418
Abstract Atherosclerosis is a complex disease that is affected by environmental as well
as genetic factors. The aim of the present study was to identify loci of
atherosclerosis susceptibility in a cross of atherosclerosis-susceptible C57BL/6
and atherosclerosis-resistant FVB/N mice on the low-density lipoprotein (LDL)
receptor (LDLR)-deficient background (LDLR(-/-)) and to test whether these loci
are affected by lineage. A total of 459 F(2)s were generated in two ways: In
cross "mB6xfFVB," male B6.LDLR(-/-) mice were crossed to female FVB.LDLR(-/-)
mice to generate 107 female and 112 male F(2)s. In cross "mFVBxfB6," male
FVB.LDLR(-/-) mice were crossed to female B6.LDLR(-/-) mice to generate 120
female and 120 male F(2)s. Animals were phenotyped for cross-sectional
atherosclerotic lesion area at the aortic root, and a genome scan was carried
out with 192 microsatellite markers. Quantitative trait locus mapping revealed
significant loci of atherosclerosis susceptibility on chromosomes 3, 10, and 12.
On chromosome 10 maximal logarithm of odds (LOD) scores of 13.1 (D10Mit16, 16
cM) and 5.7 (D10Mit168, 9 cM) were found in female and male mice, respectively.
On chromosome 3, a maximal LOD score of 5.1 (D3Mit45, 79 cM) was detected only
in females. On proximal chromosome 12 significant LOD scores were
lineage-dependent, with maximal LOD scores of 3.9 (D12Mit82, 3 cM) and 4.8
(D12Mit189, 24 cM) present only in female mice of cross mB6xfFVB and male mice
of cross mFVBxfB6, respectively. We conclude that, in this intercross, loci of
atherosclerosis susceptibility are in part sex- and lineage-dependent. Awareness
of these complexities may have major consequences for the identification of
atherosclerosis susceptibility genes by quantitative trait locus mapping.

Complications



Genes
SymbolDescription
Ldlrlow density lipoprotein receptor
D10Mit16DNA segment, Chr 10, Massachusetts Institute of Technology 16
D12Mit189DNA segment, Chr 12, Massachusetts Institute of Technology 189
D3Mit45DNA segment, Chr 3, Massachusetts Institute of Technology 45