title: Characterization of the murine Lbx2 promoter, identification of the human homologue, and evaluation as a candidate for Alström syndrome.
abstract: The murine Lbx2 gene is a member of the ladybird family of homeobox genes, which is expressed in the developing urogenital system, eye, and brain. Using transgenic mice, we demonstrate that 9 kb of the 5' flanking region of mouse Lbx2 is able to direct expression of a reporter gene in a tissue-specific manner recapitulating the endogenous expression pattern. This regulatory region provides a novel reagent allowing for transgenic expression in the developing urogenital ridge. In addition, we describe the identification of the human homologue, LBX2. Comparison of the human LBX2 and mouse Lbx2 sequences upstream of the coding regions reveals sequence conservation suggesting conserved regulatory regions. Both the human LBX2 and the mouse Lbx2 genes have similar genomic structures and are composed of two exons separated by an intron. We mapped the mouse Lbx2 gene to 35 cM on chromosome 6 and the human LBX2 gene to a homologous region of chromosome 2p13. This is a candidate region for several inherited disorders, including Alström syndrome, a disorder that includes ocular, urogenital, and renal abnormalities. Given the expression pattern of Lbx2, the chromosomal location in humans, and the potential function of mammalian ladybird genes, we have begun to analyze patients with ocular disorders and those with Alström syndrome for mutations in LBX2. Although polymorphisms were identified, our results indicate that mutations in the coding region of LBX2 do not account for Alström syndrome in the six kindreds analyzed.
authors.affiliation: Cardiology Division, Department of Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA.
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: G B
authors.initials: GB
authors.lastname: Collin
authors.forename: K C
authors.initials: KC
authors.lastname: Liu
authors.forename: D R
authors.initials: DR
authors.lastname: Beier
authors.forename: M
authors.initials: M
authors.lastname: Eccles
authors.forename: P M
authors.initials: PM
authors.lastname: Nishina
authors.forename: T
authors.initials: T
authors.lastname: Moshang
authors.forename: J A
authors.initials: JA
authors.lastname: Epstein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005123:Eye / Q000196:embryology; D005128:Eye Diseases / Q000235:genetics; D005192:Family Health; D005260:Female; D005808:Genes, Recessive; D017930:Genes, Reporter; D005820:Genetic Testing; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D017403:In Situ Hybridization; D007438:Introns; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D010375:Pedigree; D011401:Promoter Regions, Genetic; D012164:Retinal Diseases / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013577:Syndrome; D014018:Tissue Distribution
chemical_list: D018398:Homeodomain Proteins; C485667:LBX2 protein, human; C121637:Lbx2h protein, mouse