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Molecular and Cellular Biology, February 2007, p. 1370-1379, Vol. 27, No. 4
0270-7306/07/$08.00+0     doi:10.1128/MCB.01486-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Targeted Disruption of the Murine Retinal Dehydrogenase Gene Rdh12 Does Not Limit Visual Cycle Function

Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany,¹ Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, Michigan,² Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan,³ Augenklinik Campus Virchow-Klinikum Charité, Berlin, Germany,⁴ Zentrum für Molekulare Neurobiologie, Universität Hamburg, Hamburg, Germany⁵

Received 10 August 2006/ Returned for modification 22 September 2006/ Accepted 16 November 2006

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.

Published ahead of print on 27 November 2006.

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