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D. A. Thompson, K. L. Feathers, J. D. Chrispell, C. L. McHenry, P. A. Sieving, S. G. Jacobson, J. R. Heckenlively, A. Swaroop, M. I. Othman; DHRS3 (retSDR1) from the Family of Short-Chain Dehydrogenases/Reductases: Analysis of Enzyme Activity, Expression, and Sequence Variants. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1109.
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Members of the family of short-chain dehydrogenases/reductases include the retinoid dehydrogenases (RDHs) that participate in vitamin A metabolism in the retina. DHRS3 (retSDR1) was the first member of this family whose expression was localized to photoreceptor cells. The purpose of our studies was to evaluate the potential role of DHRS3 in photoreceptor retinoid metabolism and the causes of inherited retinal degeneration.
DHRS3 expression was assayed using immunohistochemical analysis with a novel anti-peptide antibody, and by quantitative PCR and microarray analysis. Retinoid dehydrogenase/reductase activity of recombinant mouse and human DHRS3 was assayed using HPLC analysis. Mutation screening was performed by sequencing DNA amplicons from over 250 individuals with autosomal recessive retinal dystrophy.
DHRS3 immunoreactivity localized to photoreceptor inner segments and the outer nuclear layer. Expression markedly increased during postnatal development in wild-type mice, but not in Nrl-deficient mice having a model all-cone retina. Assays of the dehydrogenase and reductase activity of recombinant DHRS3 showed no significant reactivity with all-trans and 11-cis retinol and retinal substrates relative to that of recombinant RDH12 assayed under the same conditions. DHRS3 sequence analysis revealed a number of common and two novel rare SNPs (R71Q, S131G), but no disease-associated variants.
The finding that DHRS3 localizes to photoreceptor inner segments and apparently does not act on visual cycle retinoid substrates revises earlier suggestions that it functions to reduce all-trans retinal in cone outer segments. Although its expression pattern suggests an important role in photoreceptor physiology, mutations in DHRS3 apparently do not contribute to the common causes of inherited retinal degeneration.
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