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J Kitamoto, DS Williams; Defective Disk Membrane Shedding In Myosin VIIa Null Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2714.
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Purpose: Mutations in the gene encoding myosin VIIa cause Usher syndrome 1B, a severe deafness-blindness disorder. To understand the cellular basis of the retinal degeneration in Usher 1B patients, we have been studying the retinas of shaker1 mice of the 4626SB allele. These mice are null Myo7a mutants, and although they do not undergo photoreceptor degeneration, their retinal phenotypes are likely to be relevant to the retinal degeneration that occurs after a decade or so in Usher 1B patients. In the present study we determined whether or not disk membrane shedding was normal. Method: Mice carrying the Myo7a(4626SB) mutation were backcrossed on to a Balb/c background and then inbred. They were reared under 12h light/12h dark cyclic lighting. Littermate heterozygous (control) and homozygous mutant mice were killed at specific times of day. Their retinas were sectioned for light microscopy, and the numbers of large phagosomes in the retinal epithelium (RPE) were counted. Results: As reported previously by others, the number of phagosomes in the RPE peaked around the time of light onset in normal animals. A peak in the number of phagosomes at this time was also found in the homozygous mutant mice. However, at times corresponding to the start of the phagosome increase (just before and at the time of light onset), phagosomes were relatively fewer in the RPE of mutant mice. Conclusion: The absence of myosin VIIa does not block disk membrane shedding. However, the kinetics of this process is perturbed, such that shedding is delayed. Although this defect does not result in photoreceptor degeneration in the shaker1 mice, the well-known importance of disk membrane shedding in photoreceptor cell viability is such that the defect we have identified is a likely candidate to contribute to photoreceptor degeneration in Usher 1B patients. Funded by NIH grant EY07042 and the Foundation Fighting Blindness. Commercial relationship disclosure:
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