@entity731 is a complex disease resulting from the interaction of multiple genes. We have used the @entity1748 knockout @entity19 model in an interspecific @entity74 to map @entity731 susceptibility loci. A total of 174 (MOLF/Ei x B6.129S7- @entity1748 (tm1Her)) x C57BL/6J- @entity1748 (tm1Her) backcross @entity19 , homozygous for the @entity1748 null allele, were fed a Western-type diet for 3 months and then killed for quantification of aortic lesions. A genome scan was carried out by using DNA pools and microsatellite markers spaced at approximately 18-centimorgan intervals. Quantitative trait locus analysis of individual backcross @entity19 confirmed linkages to chromosomes 4 ( @entity70097 , logarithm of odds = 6.2) and 6 ( @entity70098 , logarithm of odds = 6.7). @entity70097 affected lesions in females only whereas @entity70098 affected both sexes. Among females, the loci accounted for approximately 50% of the total variance of lesion area. The susceptible allele at @entity70097 was derived from the MOLF/Ei genome whereas the susceptible allele at @entity70098 was derived from C57BL/6J. Inheritance of susceptible alleles at both loci conferred a 2-fold difference in lesion area, suggesting an additive effect of @entity70097 and @entity70098 . No associations were observed between the quantitative trait loci and levels of plasma total @entity165 , high density lipoprotein @entity165 , non-high density lipoprotein @entity165 , insulin, or body weight. We provide strong evidence for complex inheritance of @entity731 in @entity19 with elevated plasma low density lipoprotein @entity165 and show a major influence of nonlipoprotein-related factors on disease susceptibility. @entity70097 and @entity70098 represent candidate susceptibility loci for @entity1 @entity731 , most likely residing on chromosomes 1p36--32 and 12p13--12, respectively.

Localization of @entity731 susceptibility loci to chromosomes 4 and 6 using the @entity1748 knockout XXXX model.

@entity1 :: ('9606', 'Species') :: ['human'] @entity1748 :: ('16835(Tax:10090)', 'Gene') :: ['Ldlr'] @entity70098 :: ('112333(Tax:10090)', 'Gene') :: ['Athsq2'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity74 :: ('MESH:D030342', 'Disease') :: ['genetic cross'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis', 'Atherosclerosis'] @entity70097 :: ('112332(Tax:10090)', 'Gene') :: ['Athsq1'] @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol']
@entity19 :: (10090,Species) :: ['mouse']
