Normal plasma lipoproteine and fertility in gene-targeted mice homozygous for a disruption in the gene encoding very low density lipoprotein receptor

Philip K. Frykman, Michael S. Brown, Tokuo Yamamoto, Joseph L. Goldstein, Joachim Herz

Research output: Contribution to journalArticle

215 Scopus citations

Abstract

The very low density lipoprotein (VLDL) receptor is a recently cloned member of the low density lipoprotein (LDL) receptor family that mediates the binding and uptake of VLDL when overexpressed in animal cells. Its sequence is 94% identical in humans and rabbits and 84% identical in humans and chickens, implying a conserved function. Its high level expression in muscle and adipose tissue suggests a role in VLDL triacylglycerol delivery. Mutations in the chicken homologue cause female sterility, owing to impaired VLDL and vitellogenin uptake during egg yolk formation. We used homologous recombination in mouse embryonic stem cells to produce homozygous knockout mice that lack immunodetectable VLDL receptors. Homozygous mice of both sexes were viable and normally fertile. Plasma levels of cholesterol, triacylglycerol, and lipoproteins were normal when the mice were fed normal, high-carbohydrate, or high-fat diets. The sole abnormality detected was a modest decrease in body weight, body mass index, and adipose tissue mass as determined by the weights of epididymal fat pads. We conclude that the VLDL receptor is not required for VLDL clearance from plasma or for ovulation in mice.

Original languageEnglish (US)
Pages (from-to)8453-8457
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number18
Publication statusPublished - Aug 29 1995

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Keywords

  • Adipose tissue
  • Body weight
  • Homologous recombination
  • Low density lipoprotein receptor gene family
  • Triacylglycerol metabolism

ASJC Scopus subject areas

  • General
  • Genetics

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