Ascla5^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Ascla5^C57BL/6J
• Name: atherosclerotic lesion area 5; C57BL/6J
• MGI ID: MGI:3613626
• QTL: Ascla5 Location: unknown Genetic Position: Chr12, cM position of peak correlated region/allele: 7.03 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 atherosclerosis susceptibility in female animals compared to FVB/N. (J:104621)
• Inheritance: Not Specified

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Candidate Genes

J:149028

Refined QTL mapping using a subset of F2 mice from the C57BL/6J-Ldlr^tm1Her X FVB/N-Ldlr^tm1Her cross (J:104621) was informative in mapping a Adam17 exon 19 SNP significantly to a the region identified as Ascla5(J:104621). The LOD score associated with the exon 19 SNP was 4.2.

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

J:104621

Linkage analysis was performed on 459 F2 animals from reciprocal between C57BL/6J-Ldlr^tm1Her and FVB/N-Ldlr^tm1Her to identify QTL associated with susceptibility to atherosclerosis. Parental strain C57BL/6J is susceptible to atherosclerosis whereas parental strain FVB/N is resistant. 154 polymorphic markers at an average spacing of 10 cM was used for the initial genome scan, and an additional set of 46 markers was used for fine mapping. Animals were fed a semisynthetic diet for 16 weeks and phenotypedfor cross-sectional atherosclerotic lesion area at the aortic root at 20 weeks of age.

The strongest linkage of LOD=13.1 mapped to 16 cM on mouse Chromosome 10 near D10Mit16. This locus is named Ascla1 (atherosclerotic lesion area 1). A previously identified QTL named Ath11 (15 cM) maps near Ascla1. A second locus named Ascla2 mapped to 9 cM near D10Mit168 with LOD=5.7. FVB/N-derived alleles confer atherosclerosis susceptibility at both QTL. Animals homozygous for FVB/N-derived alleles at Ascla1 or Ascla2 have higher mean lesion scores compared to animals homozygous for C57BL/6J-derived alleles, and the effect tends to be stronger in females.

Female-specific QTL Ascla3 mapped to 79 cM on mouse Chromosome 3 near D3Mit45 (LOD=5.1). C57BL/6J-derived alleles at Ascla3 confer atherosclerosis sucsceptibility with a codominant mode of inheritance. Female animals homozygous for C57BL/6J-derived alleles at Ascla3 exhibit 2.3-fold higher mean lesion size compared to female animals homozygous for FVB/N-derived alleles at Ascla3. Another female-specific QTL named Ascla4 mapped to 55 cM near D3Mit57. Ascla4 exhibits cross directionality and was identified in females from the (C57BL/6J-Ldlr^tm1Her x FVB/N-Ldlr^tm1Her)F2 cross. C57BL/6J-derived alleles at Ascla4 confer atherosclerosis susceptibility with a dominant mode of inheritance. Potential candidate genes for Ascla4 include Vcam1 (50.8 cM), Nfkb1 (68.9 cM), and Mttp (66.2 cM).

Two cross-specific QTL named Ascla5 and Ascla6 mapped to mouse Chromosome 12. C57BL/6J-derived alleles confer atherosclerosis susceptibility at both loci. Ascla5 is a female-specific QTL identified in the (FVB/N-Ldlr^tm1Her x C57BL/6J-Ldlr^tm1Her)F2 cross. Ascla5 is located at 3 cM near D12Mit82 (LOD=3.9). Females homozygous for C57BL/6J-derived alleles at Ascla5 exhibit 2.5-fold higher mean lesion size compared to females homozygous for FVB/N-derived alleles. A previously identified QTL named Ath6 (3 cM) maps near Ascla5. Potential candidate genes forAscla5 include Apob (3cM), Sdc1(1 cM), and Adam17 (3 cM). Ascla6 is a male-specific QTL identified in the (C57BL/6J-Ldlr^tm1Her x FVB/N-Ldlr^tm1Her)F2 cross. Ascla6 is located at 24 cM near D12Mit189 (LOD=4.8). Males homozygous for C57BL/6J-derived alleles at Ascla6 exhibit 2.7-foldhigher mean lesion size compared to males homozygous for FVB/N-derived alleles.

References

• Original: J:104621 Teupser D, et al., Atherosclerosis quantitative trait loci are sex- and lineage-dependent in an intercross of C57BL/6 and FVB/N low-density lipoprotein receptor-/- mice. Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):123-8
• All: 1 reference(s)