title: Mutant oocytic low density lipoprotein receptor gene family member causes atherosclerosis and female sterility.
abstract: The so-called very low density lipoprotein receptors (VLDLRs) are related to the LDLR gene family. So far, naturally occurring mutations have only been described for the prototype LDLR; in humans, they cause familial hypercholesterolemia. Here we describe a naturally occurring mutation in a VLDLR that causes a dramatic abnormal phenotype. Hens of the mutant restricted-ovulator chicken strain carry a single mutation, lack functional oocyte receptors, are sterile, and display severe hyperlipidemia with associated premature atherosclerosis. The mutation converts a cysteine residue into a serine, resulting in an unpaired cysteine and greatly reduced expression of the mutant avian VLDLR on the oocyte surface. Extraoocytic cells in the mutant produce higher than normal amounts of a differentially spliced form of the receptor that is characteristic for somatic cells but absent from germ cells.
authors.affiliation: Department of Molecular Genetics, Biocenter, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Bujo
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Hermann
authors.forename: J
authors.initials: J
authors.lastname: Nimpf
authors.forename: W J
authors.initials: WJ
authors.lastname: Schneider
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001161:Arteriosclerosis / Q000235:genetics*; D030161:Avian Proteins; D001483:Base Sequence; D015152:Blotting, Northern; D002462:Cell Membrane / Q000378:metabolism; D002645:Chickens / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015151:Immunoblotting; D007247:Infertility, Female / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009865:Oocytes / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface; D011973:Receptors, LDL / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000166:cytology; D014158:Transcription, Genetic; D014818:Vitellogenesis / Q000235:genetics
chemical_list: D030161:Avian Proteins; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; C096114:OVR protein, Gallus gallus; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011973:Receptors, LDL