Experiment
Two independent strain intercosses that carry atherosclerosis phenotype-sensitizing Apoe deficiency were performed to reveal artherosclerosis susceptibility loci that are distinct from loci linked to lipoprotein levels.
Animals from a C57BL/6J-derived background are susceptible to atherosclerosis and yield several-fold higher aortic lesion scores compared to animals from an FVB/NCr-derived background.
In the first cross, referred to as cross 1, B6.129P2-Apoetm1Unc x FVB.129P2-Apoetm1Bres F1 mice were crossed and the F1 offspring were intercrossed to create 197 (B6.129P2-Apoetm1Unc x FVB.129P2-Apoetm1Bres) F2 mice for the QTL analysis. Interval mapping was done with 194 markers at a distance of no more than 10cM.
In the second, confirmatory cross, B6.129P2-Apoetm1Unc x FVB.129P2-Apoetm1Bres F1 mice were crossed and the F1 offspring were intercrossed to create 186 (B6.129P2-Apoetm1Unc x FVB.129P2-Apoetm1Bres)F2 mice for QTL analysis. This cross was referred to as cross 2; these mice were genotyped using 127 markers at no more than 10cM intervals.
Interval mapping of chromosome 1, in cross 1, revealed a peak at D1Mit359, this QTL was associated with total cholesterol, HDL and LDL with LOD scores exceeding 3.5 in the combined gender groups. A peak LOD score of 6.0 was also detected at D1Mit359 for HDL in male specific data. This QTL was named Ath9. A possible candidate gene for Ath9 is Apoa2
Unexpectedly, cross 2 also revealed a suggestive linkage (LOD 3.3) for lesion formation atD1Mit359 where cross 1 did not.
The interval from 60-90 cM on mouse chromosome 1 is homologous to human 1q21-32.
Analysis Tools