Genetic analysis of murine strains C57BL/6J and C3H/HeJ to confirm the map position of Ath-1, a gene determining atherosclerosis susceptibility

Biochem Genet. 1987 Aug;25(7-8):501-11. doi: 10.1007/BF00554352.

Abstract

Previous results suggested that strains C57BL/6J and C3H/HeJ differed in a single gene for atherosclerosis susceptibility, called Ath-1. Based on data from recombinant inbred strains Ath-1 was tentatively assigned to chromosome 1 linked to Alp-2. In this report, a cross between C57BL/6 and C3H/HeJ was carried out in order to test whether the tentative map position was correct. Parental strains and F1 and F2 progeny were examined. Susceptible alleles of Ath-1, found in C57BL/6, are associated with relatively low levels of high-density lipoprotein (HDL)-cholesterol in animals fed an atherogenic diet; resistant alleles of Ath-1 are associated with relatively high levels of HDL-cholesterol. F1 progeny have HDL levels that are intermediate between these of the two parental strains. Among the F2 progeny, Alp-2 and Ath-1 cosegregated, providing confirmatory evidence that Ath-1 is linked to Alp-2 on chromosome 1. Three mice recombinant for Alp-2 and Ath-1 were found among the 60 chromosomes tested, giving an estimated map distance between these two genes of 5.0 +/- 2.8 (SE) cM. The phenotypic characteristics of Ath-1 resemble a genetic trait in humans, hyperalphalipoproteinemia, which is characterized by elevated levels of HDL-cholesterol, reduced risk of heart disease, and increased longevity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta / pathology
  • Apolipoprotein A-II
  • Apolipoproteins A / blood
  • Arteriosclerosis / genetics*
  • Arteriosclerosis / veterinary
  • Chromosome Mapping*
  • Crosses, Genetic
  • Female
  • Genetic Predisposition to Disease
  • Isoelectric Focusing
  • Lipoproteins, HDL / blood
  • Mice
  • Mice, Inbred C3H / genetics*
  • Mice, Inbred C57BL / genetics*
  • Phenotype
  • Rodent Diseases / genetics

Substances

  • Apolipoprotein A-II
  • Apolipoproteins A
  • Lipoproteins, HDL