NORMAL PLASMA-LIPOPROTEINS AND FERTILITY IN GENE-TARGETED MICE HOMOZYGOUS FOR A DISRUPTION IN THE GENE ENCODING VERY-LOW-DENSITY LIPOPROTEIN RECEPTOR

The very low density lipoprotein (VLDL) receptor is a recently cloned member of the low density lipoprotein (LDL) receptor family that media tes 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 triac ylglycerol delivery. Mutations in the chicken homologue cause female s terility, owing to impaired VLDL and vitellogenin uptake during egg yo lk 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 lipoprote ins were normal when the mice were fed normal, high-carbohydrate, or h igh-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 recepto r is not required for VLDL clearance from plasma or for ovulation in m ice.