Ath13^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Ath13^C57BL/6J
• Name: atherosclerosis 13; C57BL/6J
• MGI ID: MGI:2386546
• QTL: Ath13 Location: Chr14:47335250-47335381 bp Genetic Position: Chr14, cM position of peak correlated region/allele: 26.46 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased aortic lesion size compared to FVB/NCr. (J:76127)
• Inheritance: Dominant

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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

J:76127

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-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres F1 mice were crossed and the F1 offspring were intercrossed to create 197 (B6.129P2-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres) 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-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres F1 mice were crossed and the F1 offspring were intercrossed to create 186 (B6.129P2-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres)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 on Chromosome 14 indicated a suggestive locus in both crosses. Peak marker at D14Mit60 LOD= 3.2 in cross 1; peak marker at D14Mit63 LOD=2.5 in cross 2. Both are dominantly inherited with respect to the C57BL/6J allele; both exhibit suggestive linkage to increased aortic lesion size. The locus was labeled Ath13

The chromosome 14 interval (10-35 cM) has homology with human 14q11.2, 8p11.2 and 13q11-12. Candidate genes within this region of chromosome 14 include many proteases, including a family of mast cell proteases, metalloproteases as well ascathespin genes.

References

• Original: J:76127 Dansky HM, et al., A phenotype-sensitizing apoe-deficient genetic background reveals novel atherosclerosis predisposition Loci in the mouse. Genetics. 2002 Apr;160(4):1599-608
• All: 1 reference(s)