RDH11
Retinol dehydrogenase 11 (EC 1.1.1.300) (Androgen-regulated short-chain dehydrogenase/reductase 1) (HCV core-binding protein HCBP12) (Prostate short-chain dehydrogenase/reductase 1) (Retinal reductase 1) (RalR1) (Short chain dehydrogenase/reductase family 7C member 1) [ARSDR1] [PSDR1] [SDR7C1] [CGI-82]
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RDH11 and RDH12 are closely related retinol dehydrogenases expressed in the retina. RDH12 has been linked to the early-onset retinal dystrophy Leber congenital amaurosis, whereas RDH11 has not been associated with human disease. To understand their physiological roles, the authors investigated their expression during development and their regulation by light-induced oxidative stress in mouse retina. Quantitative RT-PCR and immunoblot analysis were used for quantification of RDH11 and RDH12 during development and oxidative stress. Expression during development was measured between embryonic day (E) 12 and postnatal day (P) 210 (7 months) in C57BL/6 mouse eyes. Expression during light-induced oxidative stress was measured between 2 and 24 hours of exposure to light in BALB/c mouse retina. The RDH11 level was low and remarkably constant during development and oxidative stress. RDH12 expression started at P7 and increased until P30 to approximately sevenfold higher than RDH11. Oxidative stress induced by exposure to constant bright light led to a rapid and significant decrease of RDH12 protein. The low and constant expression of RDH11 suggested a housekeeping function for this enzyme. The onset of RDH12 expression during the maturation of photoreceptor cells suggested a function related to the visual process. The light-induced rapid decrease of RDH12 protein, preceding the decrease of the mRNA, suggested a specific degradation of the protein rather than a regulation of gene expression.
MeSH Terms
- Aging
- Alcohol Oxidoreductases
- Animals
- Gene Expression Regulation, Developmental
- Immunoblotting
- In Situ Hybridization
- Light
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Oxidative Stress
- Oxidoreductases
- RNA, Messenger
- Radiation Injuries, Experimental
- Retina
- Retinal Degeneration
- Retinal Dehydrogenase
- Reverse Transcriptase Polymerase Chain Reaction
- Transcription, Genetic
We previously cloned mouse RDH11 (mRDH11) as a gene regulated by the transcription factor sterol regulatory element-binding proteins and showed that it is a retinol dehydrogenase expressed in non-ocular tissues such as the liver and testis and in the retina (Kasus-Jacobi, A., Ou, J., Bashmakov, Y. K., Shelton, J. M., Richardson, J. A., Goldstein, J. L., and Brown, M. S. (2003) J. Biol. Chem. 278, 32380-32389). It was proposed to function in the recycling of the visual chromophore 11-cis-retinal after photoisomerization by a bleaching light, a pathway referred to as the visual cycle. In this work, we describe our studies on the ocular function of mRDH11. We created a knockout mouse by replacing the mrdh11 coding sequence with the lacZ reporter gene for expression profiling. 5-Bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining demonstrated active transcription of this gene in photoreceptor cells. We show by immunoblot analysis that mRDH11 is associated with retinal membranes purified from a non-outer segment fraction of the retina. No obvious retinal defect was found during development and aging of RDH11-deficient mice. The functional consequences of mRDH11 disruption were investigated by electroretinography. Dark adaptation was delayed by a factor of 2.5-3 compared with wild-type mice. However, the kinetics of 11-cis-retinal recycling during dark adaptation was not affected, suggesting that mRDH11 is not involved in the visual cycle. We propose that mRDH11 disruption affects retinoid metabolism in photoreceptor inner segments and delays the kinetics of dark adaptation through modulation of calcium homeostasis.
MeSH Terms
- Aging
- Animals
- Calcium
- Chromatography, High Pressure Liquid
- DNA
- Dark Adaptation
- Drug Resistance
- Electroretinography
- Female
- Gene Expression
- Gene Expression Profiling
- Homeostasis
- Immunoblotting
- Kinetics
- Liver
- Male
- Mice
- Mice, Knockout
- Neomycin
- Oxidoreductases
- RNA, Messenger
- Retina
- Retinal Rod Photoreceptor Cells
- Retinoids
- Testis
- Transcription, Genetic
- beta-Galactosidase