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E.C. T. Oh, S. Kjellstrom, R.A. Bush, J. Bennett, P.A. Sieving, A. Swaroop; Nrl Is Sufficient for the Differentiation of Functional Rods . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3983.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The deletion of Nrl in mice results in the complete loss of rod function and super–normal cone function, mediated by S cones. Analysis of retinal gene expression profiles suggests an apparent transformation of rods into S cones in the Nrl–/– retina. Our goal is to delineate if Nrl expression is sufficient to generate rod photoreceptors from retinal progenitors/precursors. Methods: We have generated transgenic mice that express Nrl under the control of photoreceptor–specific promoters in the Nrl–null background. The phenotype of each transgenic line was analyzed at various developmental time–points by examining retinal morphology and by immunohistochemistry. Electroretinogram (ERG) studies are being used to evaluate retinal function. Subretinal Adeno–associated viral delivery of Nrl into the Nrl–null background will be performed to assess the window when Nrl can instruct the progenitors/precursors to acquire rod fate. Results: Nrl knockout mice that express the Nrl transgene under the control of Nrl, Crx or S–opsin promoter exhibit markers of rod photoreceptor development. New–born rods, as assessed by the expression of rhodopsin and the presence of outer segments with normal disks can be observed in several lines of transgenic mice. In the retina of these animals, S–opsin expression (high in the Nrl–null mice) is decreased with a concomitant increase of immunoreactivity of rod–specific proteins. ERG indicates a recovery of rod function to varying degrees, depending on the promoter used, and a partial to full return to normal cone amplitudes. Together with gene expression analysis, our results suggest the presence of functional rod photoreceptors in the transgenic mice and a reduction in the number of s–cones observed in the Nrl–null mouse retina. Conclusions: Expression of Nrl under the control of a photoreceptor promoter is sufficient to drive the expression of rod photoreceptor genes and rod phenotype. Nrl, therefore, appears to play an instructive role in rod differentiation.
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