Identification of a novel Arg-->Cys mutation in the LDL receptor that contributes to spontaneous hypercholesterolemia in pigs.

We previously carried out genetic and metabolic studies in a partially inbred herd of pigs carrying cholesterol-elevating mutations. Quantitative pedigree analysis indicated that apolipoprotein (apo)B and a second major gene were responsible for the hypercholesterolemia in these animals. In this study, we assessed LDL receptor function by three different methods: ligand blots of liver membranes using beta-very low density lipoprotein (VLDL) as a ligand; low density lipoprotein (LDL)-dependent proliferation of T-lymphocytes; and direct binding of 125I-labeled LDL to cultured skin fibroblasts.

Tissue-specific expression and cholesterol regulation of acylcoenzyme A:cholesterol acyltransferase (ACAT) in mice. Molecular cloning of mouse ACAT cDNA, chromosomal localization, and regulation of ACAT in vivo and in vitro.

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) catalyzes the esterification of cholesterol with long chain fatty acids and is believed to play an important part in the development of atherosclerotic lesions. To facilitate the study of ACAT's role in this process, we have used the human ACAT K1 clone previously described (Chang, C. C.

Apolipoprotein B and a second major gene locus contribute to phenotypic variation of spontaneous hypercholesterolemia in pigs.

The Lpb5 apolipoprotein B (apoB) allele occurs in pigs with spontaneous hypercholesterolemia. Low-density lipoprotein (LDL) from these pigs binds to the LDL receptor with a lower affinity and is cleared from the circulation more slowly than control pig LDL. However, the severity of hypercholesterolemia in pigs with the mutant apoB allele is highly variable.