title: Molecular cloning, genomic organization, genetic variations, and characterization of murine sterolin genes Abcg5 and Abcg8.
abstract: Mammalian physiological processes can distinguish between dietary cholesterol and non-cholesterol, retaining very little of the non-cholesterol in their bodies. We have recently identified two genes, ABCG5 and ABCG8, encoding sterolin-1 and -2 respectively, mutations of which cause the human disease sitosterolemia. We report here the mouse cDNAs and genomic organization of Abcg5 and Abcg8. Both genes are arranged in an unusual head-to-head configuration, and only 140 bases separate their two respective start-transcription sites. A single TATA motif was identified, with no canonical CCAT box present between the two genes. The genes are located on mouse chromosome 17 and this complex spans no more than 40 kb. Expression of both genes is confined to the liver and intestine. For both genes, two different sizes of transcripts were identified which differ in the lengths of their 3' UTRs. Additionally, alternatively spliced forms for Abcg8 were identified, resulting from a CAG repeat at the intron 1 splice-acceptor site, causing a deletion of a glutamine. We screened 20 different mouse strains for polymorphic variants. Although a large number of polymorphic variants were identified, strains reported to show significant differences in cholesterol absorption rates did not show significant genomic variations in Abcg5 or Abcg8.
authors.affiliation: Division of Endocrinology, Diabetes, and Medical Genetics, Medical University of South Carolina, Charleston, SC 29403, USA.
authors.forename: Kangmo
authors.initials: K
authors.lastname: Lu
authors.forename: Mi-Hye
authors.initials: MH
authors.lastname: Lee
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yu
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Zhou
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Sandell
authors.forename: Gerald
authors.initials: G
authors.lastname: Salen
authors.forename: Shailendra B
authors.initials: SB
authors.lastname: Patel
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002875:Chromosomes; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005091:Exons; D017353:Gene Deletion; D014644:Genetic Variation; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007438:Introns; D008074:Lipoproteins / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: C416945:ABCG5 protein, human; C462600:ABCG5 protein, mouse; C416946:ABCG8 protein, human; C462601:ABCG8 protein, mouse; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D018076:DNA, Complementary; D008074:Lipoproteins; D012333:RNA, Messenger; D005973:Glutamine