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Jerome E. Roger, Debbie F. Cheng, Norimoto Gotoh, Keerthi Ranganath, Bo Chang, Anand Swaroop; Characterization Of A New Mouse Retinal Mutant (NRM) With Immature Cone-like Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5891.
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© ARVO (1962-2015); The Authors (2016-present)
Rod and cone photoreceptors are highly differentiated neurons that convert light to an electrical signal. Their differentiation is tightly regulated by few transcription factors that include Otx2, Crx, Nrl Rorb and Nr2e3. However, the regulatory networks that control the commitment of progenitors to photoreceptor fate are poorly understood. Here, we report a new autosomal dominant retinal mutant with a unique phenotype affecting molecular signals that initiate photoreceptor fate commitment.
Fundus photography, ERG, OCT, electronic microscopy and immunohistochemistry were performed to identify and characterize the new mouse retinal mutant (Nrm). For some experiments, Nrm mice were mated with Crxp-NRL mice.
Fundus exams of 1-month old mice revealed pigmentation, attenuated vasculature and white spots, as observed in Nrl-/- and rd7 mice. These mice showed flat scotopic and photopic ERG recording. Interestingly, Muller cells were activated and photoreceptors had cone-like nuclei, an inner segment but no outer segments. However, the retina of Nrm mice did not degenerate even after 1 year. Photoreceptors did not express rod and cone opsins and the proteins involved in visual transduction pathway. Notably, high PNA immunoreactivity was observed. Since photoreceptors looked like cones, we attempted to rescue the phenotype by mating the new mutant with Crxp-NRL mice in which Crx promoter drives NRL expression in all photoreceptor precursors. A partial rescue was detected with the presence of only rod photoreceptors expressing rhodopsin but no outer segments and no recordable ERG.
This new mouse retinal mutant presents a unique phenotype with only immature cone-like photoreceptors, which surprisingly do not degenerate during aging. This mutant will potentially allow the identification of a novel key factor involved in two different biological processes: rod cell fate determination by inhibiting Nrl expression, and photoreceptor maturation by blocking outer segment formation.
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