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Publication : Targeted disruption of the mouse cis-retinol dehydrogenase gene: visual and nonvisual functions.

First Author  Shang E Year  2002
Journal  J Lipid Res Volume  43
Issue  4 Pages  590-7
PubMed ID  11907141 Mgi Jnum  J:75693
Mgi Id  MGI:2177376 Citation  Shang E, et al. (2002) Targeted disruption of the mouse cis-retinol dehydrogenase gene. Visual and nonvisual functions. J Lipid Res 43(4):590-7
abstractText  It has been proposed that cis-retinol dehydrogenase (cRDH) acts within the body to catalyze the oxidation of 9-cis-retinol, an oxidative step needed for 9-cis-retinoic acid synthesis, the oxidation of 11-cis-retinol [an oxidative step needed for 11-cis-retinal (visual chromophore) synthesis], and 3alpha-hydroxysteroid transformations. To assess in vivo the physiological importance of each of these proposed actions of cRDH, we generated cRDH-deficient (cRDH(-/-)) mice. The cRDH(-/-) mice reproduce normally and appear to be normal. However, the mutant mice do have a mild visual phenotype of impaired dark adaptation. This phenotype is evidenced by electroretinagram analysis of the mice and by biochemical measures of eye levels of retinoid intermediates during recovery from an intense photobleach. Although it is thought that cRDH is expressed in the eye almost solely in retinal pigment epithelial cells, we detected cRDH expression in other retinal cells, including ganglion cells, amacrine cells, horizontal cells, and the inner segments of the rod photoreceptor cells. Aside from the eye, there are no marked differences in retinoid levels in other tissues throughout the body for cRDH(-/-) compared with cRDH(+/+) mice. Moreover, we did not detect any non-visual phenotypic changes for cRDH(-/-) mice, suggesting that these mice do not have problems in metabolizing 3alpha-hydroxysteroids.Thus, cRDH may act essentially in the visual cycle but is redundant for catalyzing 9-cis-retinoic acid formation and 3alpha-hydroxysteroid metabolism.-Shang, E., K. Lai, A. I. Packer, J. Paik, W. S. Blaner, M. de Morais Vieira, P. Gouras, and D. J. Wolgemuth. Targeted disruption of the mouse cis-retinol dehydrogenase gene: visual and nonvisual functions. J. Lipid Res. 2002. 43: 590-597.
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