Genetic analysis of strains C57BL/6J and BALB/cJ for Ath-1, a gene determining atherosclerosis susceptibility in mice.
We previously reported that mice have at least one major gene determining atherosclerosis susceptibility, Ath-1. Susceptible alleles of Ath-1 are found in strain C57BL/6J and are associated with relatively low levels of high-density lipoprotein cholesterol (HDL-C) when these mice are fed an atherogenic diet. Resistant alleles of Ath-1 are found in strains C3H/HeJ and BALB/cJ and are associated with relatively high levels of HDL-C. Data reported earlier from the set of seven recombinant inbred (RI) strains, derived from C57BL/6By and BALB/cBy, showed that these parental strains differed at Ath-1. However, due to the limited number of RI strains, it was not possible to determine with certainty whether Ath-1 was the only major gene determining atherosclerosis susceptibility in these two strains or to determine its map position accurately. In this report, examination of F1, F2, and backcross progeny from a cross between C57BL/6J and BALB/cJ demonstrates that Ath-1 is the major gene determining atherosclerotic lesion formation and HDL-C levels in female mice. The data from male animals suggest that environmental factors or modifying genes also influence male HDL-C levels and thus partly obscure the Ath-1 phenotype. HDL-C levels in F1 progeny resemble the BALB/c parent. The data from the cross provide confirmatory evidence that Ath-1 is linked to Alp-2 on chromosome 1 with a map distance of 4.8 +/- 2.3 (SE). Combining these data with a previous cross between strain C57BL/6 and strain C3H/HeJ gives a map distance between Ath-1 and Alp-2 of 4.9 +/- 1.8 based on 7 crossovers found among 144 tested chromosomes.
Paigen
B
B
Bruce Lyon Memorial Research Laboratory, Children's Hospital Medical Center, Oakland, California 94609.
Mitchell
D
D
Holmes
P A
PA
Albee
D
D
D000483:Alleles; D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D004198:Disease Susceptibility; D005260:Female; D005796:Genes; D008297:Male; D051379:Mice; D008805:Mice, Inbred A / Q000235:genetics; D008807:Mice, Inbred BALB C / Q000235:genetics*; D008809:Mice, Inbred C3H / Q000235:genetics; D008810:Mice, Inbred C57BL / Q000235:genetics*; D010641:Phenotype; D012737:Sex Factors
D008076:Cholesterol, HDL