Homanics GE, Smith TJ, Zhang SH, Lee D, Young SG, Maeda N:
Targeted modification of the apolipoprotein B gene results in
hypobetalipoproteinemia and developmental abnormalities in mice.
Proceedings of the National Academy of Sciences of the United States of
America 1993 Mar 15;90(6):2389-93
ABSTRACT
Familial hypobetalipoproteinemia is an autosomal codominant disorder
resulting in a dramatic reduction in plasma concentrations of
apolipoprotein (apo) B, cholesterol, and beta-migrating
lipoproteins. A benefit of hypobetalipoproteinemia is that mildly
affected individuals may be protected from coronary vascular
disease. We have used gene targeting to generate mice with a
modified Apob allele. Mice containing this allele display all of the
hallmarks of human hypobetalipoproteinemia: they produce a truncated
apoB protein, apoB70, and have markedly decreased plasma
concentrations of apoB, beta-lipoproteins, and total cholesterol. In
addition, the mice manifest several characteristics that are
occasionally observed in human hypobetalipoproteinemia, including
reduced plasma triglyceride concentrations, fasting chylomicronemia,
and reduced high density lipoprotein cholesterol. An unexpected
finding is that the modified Apob allele is strongly associated with
exencephalus and hydrocephalus. These mice should help increase our
understanding of hypobetalipoproteinemia, atherogenesis, and the
etiology of exencephalus and hydrocephalus.
