Reference
Table 1- The List of 48 inbred strains used in this study:
129S1/SvImJ, C57BL/6J, I/LnJ, PERA/EiJ, A/J, C57BLKS/J, JF1/Ms, PL/J, AKR/J, C57BR/cdJ, KK/HLJ, PWK/PhJ, BALB/cByJ, C57L/J, LP/J, RBF/DnJ, BALB/cJ, C58/J, MA/MyJ, RF/J, BPH/2J, CAST/EiJ, MOLF/EiJ, RIIIS/J, BPL/1J, CBA/J, MSM/Ms, SEA/GnJ, BPN/3J, CE/J, NOD/LtJ, SJL/J, BTBR T+ tf/J, CZECHII/EiJ, NON/LtJ, SM/J, BUB/BnJ, DBA/1J, NZB/BlNJ, SPRET/EiJ, C3H/HeJ, DBA/2J, NZW/LacJ, SWR/J, C57BL/10J, FVB/NJ, P/J, WSB/EiJ.
Experiment
Males and females from 48 inbred strains were housed in two animal rooms with different health status and given an atherogenic diet. Atherosclerosis susceptibility was compared between animal rooms and between sexes and it was found that susceptibility is dependent on both health status and sex.
The data were used for associations with QTL on the mouse genome using 63,222 SNPs. Three loci in males and four loci in females were identified using the data from the low health status room. The differences between the low-status and high-status rooms were the detection of additional pathogens Pneumocystis carinii, Pasturella pneumotropica, and Helicobacter spp. in the low-status room.
Although some strains seem to have similar susceptibility in both rooms (e.g., C57BR/cdJ and BTBR T+tf/J females), many strains developed lesions only in the low-status room (males SM/J, SJL/J, SEA/GnJ, C3H/HeJ, BTBR T+tf/J, NOD/LtJ, SWR/J, C57BR/cdJ, C57BL/10J; females C57BL/6J, C57L/J, SJL/J, DBA/2J, C3H/HeJ) but not in the high status room even after longer exposure to the atherogenic diet. No significant associations were identified using the data from the high health status room.
QTL Athsq5 (atherosclerosis susceptibility QTL 5) was identified in male mice mapping to Chromosome 1 between 108,137,026 and 108,799,193 bp with a p valve of .000000034. Candidate genes mapping within the interval were Kdsr, Bc12, Serpinb5, Phlpp1 and Vps4b.
QTL Athsq6 (atherosclerosis susceptibility QTL 6) was identified in male mice mapping to Chromosome 6 between 53,791,464 and 53,903,686 bp with a p value of .00000001. A candidate gene mapping within the QTL interval was Cpvl.
QTL Athsq7 (atherosclerosis susceptibility QTL 7) was identified in male mice mapping to Chromosome 14 between 67,543,894 and 67,959,095 bp with a p value of .000000034. Candidate genes mapping within the QTL interval were Bnip3l, Ppp2r2a and Ebf2.
QTL Athsq8 (atherosclerosis susceptibility QTL 8) was identified in female mice mapping to Chromosome 2 between 109,951,892 and 110,501,333 bp with a p value of .0000007. Candidate genes mapping within the QTL interval were Ccdc34, Bbox1, Fibin, and Slc5a12.
QTL Athsq9 (atherosclerosis susceptibility QTL 9) was identified in female mice mapping to Chromosome 7 between 85,652,862 and 85,927,942 bp with a p value of .0000026. Candidate genes mapping within the QTL interval were Ntrk3, Gm9885 and Mrps11.
QTL Athsq10 (atherosclerosis susceptibility QTL 10) was identified in female mice mapping to Chromosome 18 between 58,022,123 and 58,291,010 bp with a p value of .0000025. Candidate genes mapping within the QTL interval were Slc12a2 and Fbn2.
QTL Athsq11 (atherosclerosis susceptibility QTL 11) was identified in female mice mapping to Chromosome 19 between 42,044,028 and 42,195,636 bp with a p value of .0000003. Candidate genes mapping within the QTL interval were Mms19, Ubtd1, Ankrd2, Hoga1, Mom4 and Pi4k2a.