Dual mechanisms for the low plasma levels of truncated apolipoprotein B proteins in familial hypobetalipoproteinemia. Analysis of a new mouse model with a nonsense mutation in the Apob gene.

摘要: Familial hypobetalipoproteinemia (FHbeta), a syndrome characterized by low plasma cholesterol levels, is caused mutations in the apo-B gene that interfere with synthesis of apo-B100. FHbeta frequently lead to truncated form apo-B, which typically present at < 5% levels Although many have been characterized, basic mechanisms causing variants not defined. We used targeting create mutant allele exclusively yields apo-B83. In mice heterozygous for Apob83 allele, and size density distribution apo-B83-containing lipoproteins were strikingly similar those observed humans an apo-B83 mutation. Analysis carrying mutation revealed two First, mRNA secretion reduced 76 72%, respectively. Second, was removed rapidly from plasma, compared This mouse model provides new level understanding adds insights into metabolism.