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Complementation testing with Trpm1<jats:sup>\u2212\/\u2212<\/jats:sup> mice confirmed a mutation in Trpm1. Sequencing identified a nucleotide change in exon 23, converting a highly conserved alanine within the pore domain to threonine (p.A1068T). Consistent with prior studies of Trpm1<jats:sup>\u2212\/\u2212<\/jats:sup> mice, no anatomical changes were noted in the Trpm1<jats:sup> tvrm27\/tvrm27<\/jats:sup> retina. The Trpm1<jats:sup> tvrm27\/tvrm27<\/jats:sup> phenotype is distinguished from that of Trpm1<jats:sup>\u2212\/\u2212<\/jats:sup> by the retention of TRPM1 expression on the dendritic tips of depolarizing bipolar cells (DBCs). While ERG b-wave amplitudes of Trpm1<jats:sup>+\/\u2212<\/jats:sup> heterozygotes are comparable to wild type, those of Trpm1<jats:sup>+\/ tvrm27<\/jats:sup> mice are reduced by 32%. A similar reduction in the response of Trpm1<jats:sup>+\/ tvrm27<\/jats:sup> DBCs to LY341495 or capsaicin is evident in whole cell recordings. These data indicate that the p.A1068T mutant TRPM1 acts as a dominant negative with respect to TRPM1 channel function. Furthermore, these data indicate that the number of functional TRPM1 channels at the DBC dendritic tips is a key factor in defining DBC response amplitude. The Trpm1<jats:sup> tvrm27\/tvrm27<\/jats:sup> mutant will be useful for elucidating the role of TRPM1 in DBC signal transduction, for determining how Trpm1 mutations impact central visual processing, and for evaluating experimental therapies for cCSNB. <\/jats:p>","DOI":"10.1152\/jn.00137.2012","type":"journal-article","created":{"date-parts":[[2012,8,16]],"date-time":"2012-08-16T01:11:18Z","timestamp":1345079478000},"page":"2442-2451","source":"Crossref","is-referenced-by-count":43,"title":["Depolarizing bipolar cell dysfunction due to a <i>Trpm1<\/i> point mutation"],"prefix":"10.1152","volume":"108","author":[{"given":"Neal S.","family":"Peachey","sequence":"first","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio;"},{"name":"Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio;"},{"name":"Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian N.","family":"Pearring","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, Kentucky;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Pasano","family":"Bojang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, Kentucky;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew E.","family":"Hirschtritt","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwen","family":"Sturgill-Short","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, Kentucky;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Osaka Bioscience Institute, Osaka, Japan;"},{"name":"JST CREST, Osaka Bioscience Institute, Osaka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieko","family":"Koike","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Osaka Bioscience Institute, Osaka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F. 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