Ath40^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Ath40^C57BL/6J
• Name: atherosclerosis 40; C57BL/6J
• MGI ID: MGI:5697907
• Synonyms: Atho40^{B6.129S7-Ldlrtm1Her/J}
• QTL: Ath40 Location: unknown Genetic Position: Chr8, Syntenic

Variant origin

• Strain of Specimen: B6.129S7-Ldlr^tm1Her/J

Variant description

• Allele Type: QTL

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:184168

To identify genetic loci responsible for artherosclerosis susceptibility a pool of 376 F2 mice were generated by intercrossing atherosclerosis-suscptible C57BL/6J and atherosclerosis-resistant BALB/cByJ mice on a low-density lipoprotein receptor background.

Atherosclerotic lesion size and a panel of 61 additional phenotypes were exmined in the entire F2 population. QTL mapping was performed for all 62 phenotypes.

F1 and F2 mice were generated in 2 ways:

In cross B6.129S7-Ldlr^tm1Her/J x CByJ.129S7(B6)-Ldlr^tm1Her the resulting F1s were intercrossed to generate 95 male and 95 female F2s.

In cross CByJ.129S7(B6)-Ldlr^tm1Her x B6.129S7-Ldlr^tm1Her/J the resulting F1s were intercrossed to generate 94 male and 92 female mice.

A novel QTL for atherosclerotic lesion size, Ath39, was indentified on proximal Chromosome 2. This QTL was present in male mice only with a LOD=6.18 near D2Mit27 at 28.0cM, 38.1Mb.

12.01.2015 Curator Note: Another QTL was identified on proximal Chromosome 2 in female mice which the authors also refer to as Ath39. We have named this QTL Ath47 since different LOD scores, a bimodal peak, and a different mapped location are clearly reported.

QTL Ath47 was detected in female mice with a LOD=6.20 with bimodal LOD peaks and a maximum peak near rs27192030, at 34.4 Mb.

The QTLs in both sexes were associted with 14% of the variation in atherosclerotic lesion size; and the B6 allele was determined to be the at risk allele conferring atherosclerosis susceptibility at D2Mit7 in both male and female mice [Fig 1C and 1D], with fit in both the additive and dominant mode of inheritance.

Additional QTL were identified cosegregating with traits related to lipid and sterol metabolism with Chr 2 atherosclerosis QTL Ath39 and Ath47. Highly significant QTLs, more pronounced in males, were identified:

Ptslbq1, phytosterol brassicasterol level QTL 1, LOD=5.7, p<0.001;

Lanq1, lanosterol level QTL 1, LOD=5.3, p<0.001;

Pvldlc1, plasma VLDL-cholesterol 1, LOD=3.64, p<0.03;

and Hdl8, high densitylipoprotein cholesterol (HDL) level 8, LOD=3.56, p<0.036;

which all mapping between D2Mit7 (38.1 Mb) and rs13476554 (67.1 Mb), The B6 alleles increased plasma brassicasterol, lanosterol and VLDL-C and decreased plasma HDL-C. No effect was observed for plasma LDL-C.

In addition a second novel QTL cluster was identified on Chr 8 for plasma plant sterols that colocalized with a suggestive QTL (Ath40) for atherosclerotic lesion size.

Ath40 was also a male specific QTL. It mapped with suggestive significanceto a peak near D8Mit65, LOD=3.28,p=0.09. The B6 allele displayed an additive effect, increasing atherosclerotic lesion size.

The Chromosome 8 QTL for plasma concerntrations:

Ptslbq2, phytosterol brassicasterol level QTL 2, LOD=5.29, p<0.001;

Ptslsq1, phytosterol sitosterol level QTL 1, LOD=5.86,p<0.001; and

Ptslcq1, phytosterol campesterol level QTL 1, LOD=3.28,p=0.09 also mapped near D8Mit65. This cluster was also male specific. The B6 allele displayed an additive effect increasing plasmalevels of phytosterols.

References

• Original: J:184168 Burkhardt R, et al., Cosegregation of aortic root atherosclerosis and intermediate lipid phenotypes on chromosomes 2 and 8 in an intercross of C57BL/6 and BALBc/ByJ low-density lipoprotein receptor-/- mice. Arterioscler Thromb Vasc Biol. 2011 Apr;31(4):775-84
• All: 1 reference(s)