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MM LaVail, W Feng, D Yasumura, MT Matthes, N Trautmann, JL Duncan, H Yang, HS Earp, GK Matsushima, D Vollrath; Mer Knockout Mice Display an RCS-Like Retinal Dystrophy Phenotype . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2709.
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Purpose: To determine if mice that are homozygous for a targeted disruption (merkd) of the Mer receptor tyrosine kinase gene manifest a retinal dystrophy phenotype similar to that of the RCS rat, which carries a mutated Mertk gene. Methods: The presence or absence of Mertk protein in tissues of merkd mice was assessed by immunoblot analysis. Eyes of merkd and C57BL/6 wild-type (WT) mice were examined by light and electron microscopy at ages ranging from postnatal day (P) 8 to 8 months. Results: Homozygous merkd mice lack Mertk protein and show a phenotype very similar to that of RCS rats. Features of the phenotype common to the two mutant strains include the apparent absence of phagosomes in the retinal pigment epithelium (RPE) at the peak of disk shedding, longer than normal outer segments (OS) at early ages, disorganization and accumulation of membranous debris and whorls of membranes at the RPE-OS interface, photoreceptor (PR) degeneration and loss in an asymmetric pattern between superior and inferior hemispheres, and a relatively slow removal of pyknotic PR nuclei. Most PRs are missing and OS debris is removed by about P60-P80, similar to the course of degeneration in RCS rats. Like RCS rats, heterozygous merkd mice have normal retinal structure, indicating that the retinal dystrophy trait is completely recessive. Conclusions: Ablation of Mertk function in merkd mice results in a retinal phenotype almost identical to that of the RCS rat. The similarity in phenotypes between the mouse and rat models suggests that an RPE phagocytic defect underlies human retinitis pigmentosa caused by MERTK mutations. Support: Grants from the NIH, the Foundation Fighting Blindness, the Ruth and Milton Steinbach Fund, the Karl Kirchgessner Foundation, That Man May See, Inc., Macula Vision Research Foundation and Research to Prevent Blindness.
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