MUTANT OOCYTIC LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE FAMILY MEMBER CAUSES ATHEROSCLEROSIS AND FEMALE STERILITY

The so-called very low density lipoprotein receptors (VLDLRs) are rela ted to the LDLR gene family. So far, naturally occurring mutations hav e only been described for the prototype LDLR; in humans, they cause fa milial hypercholesterolemia. Here we describe a naturally occurring mu tation in a VLDLR that causes a dramatic abnormal phenotype. Hens of t he mutant restricted-ovulator chicken strain carry a single mutation, lack functional oocyte receptors, are sterile, and display severe hype rlipidemia with associated premature atherosclerosis. The mutation con verts a cysteine residue into a serine, resulting in an unpaired cyste ine and greatly reduced expression of the mutant avian VLDLR on the oo cyte surface. Extraoocytic cells in the mutant produce higher than nor mal amounts of a differentially spliced form of the receptor that is c haracteristic for somatic cells but absent from germ cells.