Ath37^CAST/Ei
QTL Variant Detail

Summary

• QTL variant: Ath37^CAST/Ei
• Name: atherosclerosis 37; CAST/Ei
• MGI ID: MGI:3639872
• QTL: Ath37 Location: Chr6:116641858-128495988 bp Genetic Position: Chr6, cM position of peak correlated region/allele: 53.83 cM
• QTL Note: genome coordinates based on the boundaries of the QTL region

Variant origin

• Strain of Specimen: CAST/Ei

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers resistance to atherosclerotic lesions compared to C57BL/6J. (J:109792)

Notes

Ath37 and Ath38 may interact epistatically.

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

J:109792

Previously identified arterial lesion susceptibility QTL Artles (arterial lesions) mapped to 61 cM on mouse Chromosome 6. This locus was refined into 2 separate QTL designated Ath37 and Ath38 using 16 different interval specific congenic strains derived from B6.CAST-(D6Mit102-D6Mit198) Ldlr^tm1Her, also referred to as CON6. At 12 weeks of age, female animals were placed on a Western high fat diet for a duration of 8 weeks.

The proximal locus Ath37 spans a 12.1 Mb interval between D6Mit115 (51 cM) and D6Mit61 (62.3 cM). Adipor2 (60.7 cM), A2m (61.7 cM), and Cd163 are potential candidate genes mapping near Ath37. The distal locus Ath38 spans a 7.8 Mb interval between D6Mit61 (62.3 cM) and D6Mit258 (65.5 cM). Olr1 is a potential candidate gene for Ath38. CAST/Ei-derived alleles at Ath37 and Ath38 confer reduced atherosclerotic lesion size on a high fat diet by 43% and 41%, respectively. These loci may interact epistatically.

A 13.1 Mb region on the telomeric end of chromosome 6 also shows evidence for harboring at least 2 other genes involved in susceptibility to atherosclerotic lesions. The 2 genes appear to have opposite effects, where CAST/Ei-derived alleles at one confers protection and CAST/Ei-derived alleles at the other confers susceptibility.

Alox5 (53.2 cM), a candidate gene for Artles, maps proximal to both Ath37 and Ath38. Animals homozygous for the Alox5^tm1Fun knockout allele exhibit 10-fold reduced atherosclerosis on a high fat diet compared to C57BL/6J controls. However, homozygosity for CAST/Ei Alox5 alleles does not decrease the frequency of aortic aneurysms as hypothesized.

References

• Original: J:109792 Ghazalpour A, et al., Complex inheritance of the 5-lipoxygenase locus influencing atherosclerosis in mice. Genetics. 2006 Jun;173(2):943-51
• All: 1 reference(s)