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Neal S. Peachey, Maureen A. McCall, Regina D. Nobles, Matthew A. Hirschtritt, Jillian N. Pearring, Pasano Bojang, Jr., Yin Shen, Scott A. Nawy, Patsy M. Nishina, Ronald G. Gregg; Trpm1 Point Mutation Underlies Retinal Dysfunction In The Mtvr27 Mouse Model Of Complete Congenital Stationary Night Blindness. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4124.
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© ARVO (1962-2015); The Authors (2016-present)
Using an ERG screen of ENU-mutagenized C57BL/6J mice to identify new vision mutants, mutant Mtvr27 was identified due to the absence of the b-wave component while the a-wave was present. Here we identify the gene involved and define the retinal phenotype of the mutant.
Linkage mapping, complementation mating, and candidate gene sequencing identified the Mtvr27 gene. Retinal electrophysiology was evaluated by ERG, whole cell patch clamp analysis of bipolar cell responses to a glutamate agonist in an in vitro slice preparation and in vivo RGC single cell electrophysiology. Retinal anatomy was evaluated by immunohistochemistry and confocal microscopy.
The Mtvr27 locus mapped to a region of Chr. 7 that contains Trpm1. Offspring generated by crossing Mtvr27 and Trpm1-/- mice had a normal ERG a-wave but no b-wave indicating that Mtvr27 is a new Trpm1 allele. A point mutation (Ala952Thr) was identified in Trpm1Mtvr27. Overall retinal structure appears normal in Trpm1Mtvr27 mice. A rabbit polyclonal antibody against TRPM1 (Sigma) labels the OPL in Trpm1Mtvr27 but not Trpm1-/- retina. Trpm1Mtvr27 DBCs do not respond to puffs of the mGluR6 antagonist LY341495. Differences are found in the light evoked responses of Trpm1Mtvr27 RGCs when compared to C57B6/J RGCs that include abnormal receptive field organization and the presence of spontaneous rhythmic bursting. Dark-adapted ERGs of Trpm1Mtvr27 mice contain a small low intensity response that is absent in Trpm1-/- animals.
The Mtvr27 mutant is caused by a mutation in the Trpm1 gene. The phenotype of Trpm1Mtvr27mutant mice resembles that of the Trpm1-/- in many ways, but is distinguished by the retention of TRPM1 protein expression in the OPL and a residual ERG response at low intensities.
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