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V. R. Chavali, N. W. Khan, D. U. Bartsch, M. M. Jablonski, R. Ayyagari; Gene Knock-In Mouse Model for Late-Onset Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6141.
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Autosomal dominant late-onset retinal degeneration (L-ORD) in humans is caused by a S163R mutation in the human C1QTNF5/CTRP5 gene. To understand the molecular basis of pathology in L-ORD, a knock-in mouse model carrying the CTRP5 S163R mutation (Ctrp5_mut+/-) in the heterozygous state was generated and its retinal phenotype was characterized.
Expression of CTRP5 wild type and mutant transcripts and protein was detected in mutant mice. Fundus examination of the mutant mice revealed no changes until age 12 months. Morphological analysis revealed abnormalities in the photoreceptor layer with no accumulation of sub-RPE debris. TEM showed abnormalities in the RPE, disorganized outer segments and swollen inner segments. These morphological changes were found to be progressive with an onset around age 8 months. By this age selected photoreceptor genes were found to be expressed at low levels in the Ctrp5_mut+/- mice retina when compared with the wild type mice. Scotopic and photopic ERG responses were comparable to wild type until 12 months age. At 13 months, ERG amplitudes showed a modest decline.
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