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J. Rozet, I. Perrault, K. Bigot, A. Provot, L. Vede, A. Munnich, M. Abitbol, J. Kaplan; Histological Findings in GUCY2D–/– x PDERd10/rd10 Double Mutant Mice Suggest a Protective Effect of cGMP Depletion in Photoreceptors Lacking Rod–Specific PDE Function . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1049.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize the phenotype of a mouse lacking both GUCY2D and rod–specific PDE functions.
GUCY2D knock–out mice were crossed with homozygous PDERD10/RD10 mice to generate double mutant GUCY2D–/– x PDERD10/RD10 mice. Comparative histological studies of the retinas of rd10 and double mutant mice were performed at ages 2, 3, 4, 5, 6, 7 weeks. For that purpose, the animals’ eyes were fixed in paraformaldehyde, embedded in wax, sectioned at 4µm and coloured in HES.
As soon as 4 weeks of age, the retinas of homozygous PDERD10/RD10 mice showed a massive reduction of OS, IS and ONL. Conversely, the retina of double mutant mice of the same age demonstrated slower photoreceptor degeneration. In PDERD10/RD10 mice a dramatic degeneration was noted in both central and peripheral retina (one or two rows of photoreceptors). In double mutant mice the degeneration followed a concentric gradient from the central retina to the peripheral retina where a significant number of photoreceptors was still present up to 7 weeks of age, especially in the superior retina.
It has been shown that the invalidation of GUCY2D in mice resulted in cone degeneration but not rods that remain normal and functional. On the other hand, the missense mutation in the rod–specific beta–subunit of the PDERD10/RD10 mice resulted in a fast degeneration of both rods and cones. Interestingly, in mice lacking both the GUCY2D and PDE functions, the degeneration of photoreceptors was less severe than in rd10 mouse. Although preliminary, these data suggest that the retinal–specific guanylate cyclase gene might play a role in rod photoreceptors of mouse and that the lowering of cGMP synthesis might partially protect these cells from degeneration. Histological studies will be extended to older mice and electrophysiological studies will be performed.
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