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L.D. Wicker, A. Kasus–Jacobi; RDH11 and RDH12: Localization and Relative Expression Levels in the Mouse Retina . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4877.
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RDH12 mutations cause Leber Congenital Amaurosis (LCA), the most early onset form of retinal dystrophy. This gene is specifically transcribed in photoreceptor cells and encodes a retinol dehydrogenase exhibiting an unusual double substrate specificity towards retinaldehydes and lipid peroxidation products (short–chain aldehydes). The enzyme most closely related to RDH12 is RDH11, which is also expressed in photoreceptor cells, has the same double substrate specificity, and is important for visual function. In this study, we investigated if both enzymes could have redundant functions in vivo, by comparing their localization and expression levels in mouse retina.
Protein localization was examined in mouse retina by immunofluorescence and confocal microscopy. Mouse retinas were also fractionated in rod outer segment (ROS) and rest of the retina (RR) in discontinuous sucrose gradient and analyzed by immunoblot. Expression levels were compared in mouse retina and other tissues by quantitative RT–PCR and immunoblot analysis.
RDH11 was found strictly located in photoreceptor inner segments, and RDH12 was mostly located in photoreceptor inner segments and cell bodies. In the retina, the mRNA level of rdh12 was 6–fold higher than rdh11, while in all other tissues examined, rdh11 was higher than rdh12. At the protein level, RDH12 was only detected in the retina, where it was estimated to be more than 40–fold more abundant than RDH11.
The fact that RDH11 and RDH12 have the same substrate specificity and are both located in the inner segments of photoreceptor cells suggests that they have overlapping functions in vivo. The 40–fold higher expression of RDH12 compared to RDH11 could explain why RDH11 cannot compensate for the loss of RDH12 in LCA patients. It also suggests that elevation of RDH11 levels may partly or completely prevent the progression of LCA.
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