title: Targeted disruption of the murine retinal dehydrogenase gene Rdh12 does not limit visual cycle function.
abstract: RDH12 codes for a member of the family of short-chain alcohol dehydrogenases/reductases proposed to function in the visual cycle that supplies the chromophore 11-cis retinal to photoreceptor cells. Mutations in RDH12 cause severe and progressive childhood onset autosomal-recessive retinal dystrophy, including Leber congenital amaurosis. We generated Rdh12 knockout mice, which exhibited grossly normal retinal histology at 10 months of age. Levels of all-trans and 11-cis retinoids in dark- and light-adapted animals and scotopic and photopic electroretinogram (ERG) responses were similar to those for the wild type, as was recovery of the ERG response following bleaching, for animals matched for an Rpe65 polymorphism (p.L450M). Lipid peroxidation products and other measures of oxidative stress did not appear to be elevated in Rdh12(-/-) animals. RDH12 was localized to photoreceptor inner segments and the outer nuclear layer in both mouse and human retinas by immunohistochemistry. The present findings, together with those of earlier studies showing only minor functional deficits in mice deficient for Rdh5, Rdh8, or Rdh11, suggest that the activity of any one isoform is not rate limiting in the visual response.
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Butenfeld 42, 22529 Hamburg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Kurth
authors.forename: Debra A
authors.initials: DA
authors.lastname: Thompson
authors.forename: Klaus
authors.initials: K
authors.lastname: Rüther
authors.forename: Kecia L
authors.initials: KL
authors.lastname: Feathers
authors.forename: Jared D
authors.initials: JD
authors.lastname: Chrispell
authors.forename: Jana
authors.initials: J
authors.lastname: Schroth
authors.forename: Christina L
authors.initials: CL
authors.lastname: McHenry
authors.forename: Michaela
authors.initials: M
authors.lastname: Schweizer
authors.forename: Sergej
authors.initials: S
authors.lastname: Skosyrski
authors.forename: Andreas
authors.initials: A
authors.lastname: Gal
authors.forename: Christian A
authors.initials: CA
authors.lastname: Hübner
mesh_terms: D000429:Alcohol Oxidoreductases; D000818:Animals; D004596:Electroretinography; D005786:Gene Expression Regulation; D018390:Gene Targeting; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018384:Oxidative Stress; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000172:deficiency / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D012176:Retinoids / Q000032:analysis; D014785:Vision, Ocular / Q000235:genetics / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D012176:Retinoids; D000429:Alcohol Oxidoreductases; C517812:Rdh12 protein, mouse; D050697:Retinal Dehydrogenase