Genetic control of hepatic apoB-100 secretion in human apoB transgenic mouse strains

Plasma apolipoprotein B (apoB) levels vary widely in the general population and elevated plasma levels of apoB are associated with higher risk for ath erosclerotic coronary heart disease, Determination of genetic factors regul ating population variance of plasma apoB levels is complicated by the genet ic heterogeneity of human populations. Using a congenic human apoB transgen ic mouse strain in the C57BL/6 background (B6 HuBTg), we assessed genetic e ffects on the variance of plasma apoB, and on hepatic apoB-100 secretion ra tes. Six inbred mouse strains were crossed with the B6 HuBTg strain, Mean p lasma apoB levels in the parental B6 HuBTg strain were 95 +/- 14 mg/dl, F1 human apoB transgenic offspring displayed plasma human apoB levels 1 rangin g from 60 to 105 mg/dl. In three F1 strains, the BALB/B6, C3H/B6 and 129/B6 strains, markedly lower plasma apoB levels (61 +/- 11, 64 +/- 5, and 67 +/ - 8 mg/dl) were due to lower apoB-100 secretion rates. Human apoB mRNA leve ls in these three F1 strains were similar to those of the parental B6 strai n suggesting that the mechanism for varying apoB secretion rates is most li kely not transcriptional. In summary, we have identified three inbred mouse strains possessing polymorphic alleles which, when crossed with the B6 str ain, lower plasma apoB levels and apoB-100 secretion in their F1 offspring, These mouse strains provide a powerful tool for genetic analysis of factor s regulating apoB-100 secretion and hence plasma apoB levels.