Atherosclerosis susceptibility loci identified from a strain intercross of apolipoprotein E-deficient mice via a high-density genome scan.
OBJECTIVE
Apolipoprotein (apo) E-deficient mice are hypercholesterolemic and develop atherosclerosis on low-fat chow diets; however, the genetic background strain has a large effect on atherosclerosis susceptibility. This study aimed to determine the genetic regions associated with strain effects on lesion area.


RESULTS
We performed a strain intercross between atherosclerosis sensitive DBA/2 and atherosclerosis resistant AKR apoE-deficient mice. Aortic root lesion area, total cholesterol, body weights, and complete blood counts were ascertained for 114 male and 95 female F2 progeny. A high-density genome scan was performed using a mouse single nucleotide polymorphism chip yielding 1967 informative polymorphic markers. Quantitative trait locus (QTL) statistical analyses were performed. Novel loci associated with lesion or log lesion area were identified for the female and male F2 cohorts. The atherosclerosis QTLs in female mice reside on chromosomes 15, 5, 3, and 13, and in male mice on chromosomes 17, 18, and 2. QTL were also identified for body weight, total cholesterol, and blood count parameters.


CONCLUSIONS
Loci were identified for atherosclerosis susceptibility in a strain intercross study. The identity of the responsible genes at these loci remains to be determined.
Smith
Jonathan D
JD
Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio, USA. smithj4@ccf.org
Bhasin
Jeffrey M
JM
Baglione
Julie
J
Settle
Megan
M
Xu
Yaomin
Y
Barnard
John
J
D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D023281:Genomics; D005838:Genotype; D008126:Lod Score; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D013045:Species Specificity
D001057:Apolipoproteins E; D005819:Genetic Markers