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Variant description |
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Phenotypes |
View phenotypes and curated references for all genotypes (concatenated display).
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Expression |
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Notes |
Mapping and Phenotype information for this QTL, its variants and associated markersJ:70961Genome scan at an average marker density of 10 cM was performed on approximately 250 (CAST/Ei x C57BL/6J)F2 animals to identify QTLs associated with arterial lesion formation. Animals were places on a 15 week atherogenic diet at 4 months of age. Parental strain CAST/Ei is resistant to atherosclerosis when placed on an atherogenic diet whereas parental strain C57BL/6J is susceptible. A significant QTL associated with arterial lesion formation and insulin level, Artles, mapped to approximately 61 cM on mouse Chromosome 6 with a maximum LOD score 6.7 near D6Mit256. Artles spans an interval of 38.5 cM - 67 cM and appears to be inherited in a codominant fashion. Artles was confirmed in congenic strains carrying CAST/Ei-derived DNA spanning 38.5 cM - 67 cM ofmouse Chromosome 6 (D6Mit102 to D6Mit198) on a C57BL/6J background. The congenics exhibited similar resistance to arterial lesions as donor strain CAST/Ei. The same protective effect was observed in a congenic strain carrying the same CAST/Ei-derived region (38.5 cM-67 cM of mouse Chromosome 6) on a highly susceptible LDLR -/- background. Possible candidate genes in the region of Artles include Pparg and Apobec1. J:109792Previously 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) Ldlrtm1Her, 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 Alox5tm1Fun 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. |
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References |
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 12/10/2024 MGI 6.24 |
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