Genetic factors in lipoprotein metabolism. Analysis of a genetic cross between inbred mouse strains NZB/BINJ and SM/J using a complete linkage map approach.

A genetic cross was constructed from two parental inbred strains of mice, NZB/BINJ and SM/J, which differ markedly in their plasma lipoprotein levels. Plasma lipid and apolipoprotein values were measured in 184 F2 progeny on a normal chow diet and on an atherogenic diet. Genetic markers were typed at 126 loci spanning all chromosomes except the Y. Statistical analysis revealed significant linkage or suggestive linkage of lipoprotein levels with markers on a number of chromosomes. Chromosome 1 markers were linked to levels of total cholesterol (lod 5.9) and high density lipoprotein (HDL) cholesterol (lod 8.1), chromosome 5 markers were linked to levels of total cholesterol (lod 6.7) and HDL cholesterol (lod 5.6), and chromosome 7 markers were linked to levels of total plasma triglycerides (lod 5.1) and free fatty acids (lod 5.6). Plasma apoAII levels were linked to the apoAII gene (lod score 19.6) and were highly correlated with plasma HDL cholesterol levels (r = 0.63, P = 0.0001), indicating that apoAII expression influences HDL cholesterol levels. Molecular studies suggested that structural differences in the apoAII polypeptide of the two strains may contribute to differences in clearance of the protein.