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L.H. Pinto, M. Vitaterna, S. Siepka, K. Shimomura, W. Kibbe, R. Mullins, E. Heffron, E. Stone, V. Sheffield, J.S. Takahashi; Mapping and Characterization of Noerg–1 Mutation in Mouse . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4753.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:The dominant Noerg–1 mutation was generated by chemical mutagenesis and causes loss of the ONL in 12 week old mice. We wished to determine the mechanism for cell death and to map the mutation genetically. Methods: At 8–12 weeks of age the dark– adapted electroretinogram of 28 G5 mice was measured and quantified, the fundus was photographed and analyzed for abnormalities and the retina was examined with immunofluorescence and TUNEL analysis. 70 mutant offspring of a mapping crosses with the DBA/2J and BALB/c strains were analyzed with informative SNP and SSLP markers. Results: A significant degree of photoreceptor degeneration and reduction of the amplitude of the rod components of the ERG were apparent by 8 weeks of age. The outer nuclear layer in Noerg–1 mice was reduced to 2 to 7 rows of nuclei. Photoreceptor inner and outer segments were attenuated in young Noerg–1 mice, with some PNA and anti–rhodopsin labeling of shortened outer segments. TUNEL–positive nuclei were detected in the ONL of Noerg–1 mice. The RPE, inner nuclear layer and ganglion cell layer were intact. The mutation mapped to Chromosome 6, distal to D6Mit287 (112.8 MB, 2/70 recombinants) and proximal of D6Mit254 (121.8 MB, 5/70 recombinants). Conclusions: Histological analyses suggest that Noerg–1 mutation leads to photoreceptor degeneration and that photoreceptor cells die by apoptosis. Genetic analysis shows that the gene responsible for the phenotype lies in a region of the chromosome containing the genes encoding rhodopsin, a number of membrane transporters, and several novel genes.
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