title: Cloning and characterization of the murine Vmd2 RFP-TM gene family.
abstract: Mutations in the human vitelliform macular dystrophy type 2 (VMD2) gene are known to cause autosomal dominant Best macular dystrophy (BMD), a degenerative disorder of the central retina. VMD2, together with VMD2L1, VMD2L2 and VMD2L3, belong to a closely related gene family characterized by several transmembrane (TM) spanning helical domains and an invariant arginine, phenylalanine and proline (RFP) tripeptide motif, thus termed VMD2 RFP-TM. The four genes are thought to encode a novel family of anion channels. We now report the cloning and characterization of the murine orthologs by combining biocomputational analyses and molecular genetic approaches. While the murine Vmd2, Vmd2l1 and Vmd2l3 genes are functional, murine Vmd2l2p was found to be a non-transcribed pseudogene. Expression profiling of the murine Vmd2 RFP-TM family members revealed tissue-restricted expression with predominant transcription of Vmd2 in testis, of Vmd2l1 in colon and of Vmd2l3 in heart. Differential splicing was observed for Vmd2l3 in a number of tissues (e.g. in brain, retina/RPE, kidney) although the functional importance of the splice variants remains to be determined.
authors.affiliation: Institut für Humangenetik, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Krämer
authors.forename: H
authors.initials: H
authors.lastname: Stöhr
authors.forename: B H F
authors.initials: BH
authors.lastname: Weber
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D000075002:Bestrophins; D018118:Chloride Channels; D019976:Cloning, Organism; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics; D030541:Databases, Genetic; D020224:Expressed Sequence Tags; D005136:Eye Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D007473:Ion Channels; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D044767:Ubiquitin-Protein Ligases; D000070584:Tripartite Motif Proteins
chemical_list: D000075002:Bestrophins; D018118:Chloride Channels; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D007473:Ion Channels; D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; C113133:BEST1 protein, human; C491856:Best1 protein, mouse; C497463:Best2 protein, mouse; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins; C491853:Vmd2L3 protein, mouse; C489296:Trim27 protein, mouse