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M. Bustamante, S. Cottet, D. F. Schorderet; Reduced Expression of Myo7a May Be Responsible for Abnormal Opsin Distribution in Rpe65-/- Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2982. doi: https://doi.org/.
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Microarray analysis of rpe65-/- mice showed downregulation of several genes compared to wild type mice. One of them, Myo7a, a gene coding for an unconventional myosin, was shown to be implicated in Usher I syndrome, a disease characterized by deafness and retinitis pigmentosa. Studies showed that rod opsin mutations also lead to retinitis pigmentosa. Rpe65-/- shows an early retinal degeneration and opsin distribution may play a role in this process. Myo7a has been shown to play a role in opsin distribution from the cell body to the outer segment of the photoreceptor cell.The aim of the study is to assess the role played by Myo7a in the retinal degeneration observed in the rpe65-/- mice.
rpe65-/- mice were analyzed at 2-, 6- and 8-month of age. Retinas were removed and RNA was isolated with the Trizol reagent according to manufacturer’s instructions. Real-time PCRs were performed for Myo7a and other genes of interest.
Myosin7a alignment in different species all show conserved IQ motifs; FERM, MyTH4 and SH3 domains. Microarray results show a reduction of Myo7a expression in rpe65-/- mice compared to wild type at any age tested. We observed a 3-fold reduction of Myo7a expression at 6 month-old knockout mice. This reduced expression was confirmed by Real-Time PCR experiments.
In photoreceptor, many processes act as opsin-dependent cell death initiator. Two of them are the degradation of mislocalized opsins and the interference with vesicular traffic; two mechanisms in which Myo7a is known to directly or indirectly play a role. In conclusion, RPE dysfunction may also involve abnormal distribution of opsin in photoreceptor cells through Myo7a which in turn may participate to retinal degeneration in rpe65-/- mice.
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