Quantitative trait locus analysis of neointimal formation in an intercross between C57BL/6 and C3H/HeJ apolipoprotein E-deficient mice.
BACKGROUND
Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) exhibit marked differences in neointimal formation after arterial injury when deficient in apolipoprotein E (apoE(-/-)) and fed a Western diet. Quantitative trait locus (QTL) analysis was performed on an intercross between B6.apoE(-/-) and C3H.apoE(-/-) mice to determine genetic factors contributing to the phenotype.


RESULTS
Female B6.apoE(-/-) mice were crossed with male C3H.apoE(-/-) mice to generate F(1)s, which were intercrossed to generate 204 male F(2) progeny. At 10 weeks of age, F(2)s underwent endothelium denudation injury to the left common carotid artery. Mice were fed a Western diet for 1 week before and 4 weeks after injury and analyzed for neointimal lesion size, plasma lipid and MCP-1 levels. One significant QTL, named Nih1 (61cM, LOD score: 5.02), on chromosome 12 and a suggestive locus on chromosome 13 (35cM, LOD: 2.67) were identified to influence lesion size. One significant QTL on distal chromosome 1 accounted for major variations in plasma non-HDL cholesterol and triglyceride levels. Four suggestive QTLs on chromosomes 1, 2, and 3 were detected for circulating MCP-1 levels. No correlations were observed between neointimal lesion size and plasma lipid levels or between lesion size and plasma MCP-1 levels.


CONCLUSIONS
Neointimal formation is controlled by genetic factors independent of those affecting plasma lipid levels and circulating MCP-1 levels in the B6 and C3H mouse model.
Yuan
Zuobiao
Z
Department of Radiology, University of Virginia, Charlottesville, VA 22908, USA.
Pei
Hong
H
Roberts
Drew J
DJ
Zhang
Zhimin
Z
Rowlan
Jessica S
JS
Matsumoto
Alan H
AH
Shi
Weibin
W
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D001483:Base Sequence; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000097:blood; D005260:Female; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism
D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D008055:Lipids; D050986:YY1 Transcription Factor