Absence of hyperlipidemia in LDL receptor-deficient mice having apolipoprotein B100 without the putative receptor-binding sequences.

ABSTRACT:

Objective

To examine the effects of apoB100 structure, specifically a mutation in the LDLr binding region, on the production of LDL and development of atherosclerosis in vivo.

Methods and results

Ldlr(-/-)Apobec1(-/-) mice lacking the LDLR and apoB editing enzyme accumulated LDL in plasma and developed severe atherosclerosis when they had wild-type apoB100. In marked contrast, in Ldlr(-/-)Apobec1(-/-) mice carrying the Apob100-beta mutation, in the 2 putative LDLR-binding domains of apoB prevented both LDL accumulation and atherosclerosis. Intestinal absorption of lipids and triglyceride secretion from the liver were not affected. However, the VLDL particles with apoB100-beta were larger in volume by about 70%, and carried approximately four times as much apoE per particle.

SUBMITTER: Johnson LA 

PROVIDER: S-EPMC5268125 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature