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 mi ce, NZB/B1NJ and SM/J, which differ markedly in their plasma lipoprote in 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 linkag e of lipoprotein levels with markers on a number of chromosomes, Chrom osome 1 markers were linked to levels of total cholesterol (led 5.9) a nd high density lipoprotein (HDL) cholesterol (led 8.1), chromosome 5 markers were linked to levels of total cholesterol (led 6.7) and HDL c holesterol (led 5.6), and chromosome 7 markers were linked to levels o f total plasma triglycerides (led 5.1) and free fatty acids (led 5.6), Plasma apoAII levels were linked to the apoAII gene (led score 19.6) and were highly correlated with plasma HDL cholesterol levels (r = 0.6 3, P = 0.0001), indicating that apoAII. expression influences HDL chol esterol levels, Molecular studies suggested that structural difference s in the apoAII polypeptide of the two strains may contribute to diffe rences in clearance of the protein.