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Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase ß subunit

Lem, Janis and Flannery, John G. and Li, Tiansen and Applebury, Meredithe L. and Farber, Debora B. and Simon, Melvin I. (1992) Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase ß subunit. Proceedings of the National Academy of Sciences of the United States of America, 89 (10). pp. 4422-4426. ISSN 0027-8424. PMCID PMC49094. doi:10.1073/pnas.89.10.4422.

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The ß subunit of the cGMP phosphodiesterase (PDE) gene has been identified as the candidate gene for retinal degeneration in the rd mouse. To study the molecular mechanisms underlying degeneration and the potential for gene repair, we have expressed a functional bovine cGMP PDE ß subunit in transgenic rd mice. One transgenic mouse line showed complete photoreceptor rescue across the entire span of the retina. A second independently derived line showed partial rescue in which photoreceptors in the superior but not the inferior hemisphere of the retina were rescued. In the latter animals, intermediate stages of degeneration were observed in the transition zone between rescued and diseased photoreceptors. Pathologic changes in the retina ranged from vesiculation of the basalmost outer segment discs in otherwise structurally intact rod cells to photoreceptors with highly disorganized outer segments and intact inner segments. Totally or partially rescued retinas showed a corresponding restoration of cGMP PDE activity, whereas nonrescued retinas had minimal enzyme activity, characteristic of the rd phenotype. These transgenic animals provide models for studying the molecular basis of retinal degenerative disease and conclusively demonstrate that the phenotype of rd mice is produced by a defect in the ß subunit of cGMP PDE.

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Additional Information:© 1992 by the National Academy of Sciences. Contributed by Melvin I. Simon, February 18, 1992. Special thanks to J. Chen and C. Bowes for helpful discussion, P. Overbeek for suggesting the FVB/n mouse line, and J. Liang and C. Yamashita for technical assistance. This work was supported in part by National Institutes of Health Program Project AG97687 (M.I.S.), National Institutes of Health Grant EY08285 (to D.B.F.) and Grant EY940801 (to M.L.A.), an unrestricted departmental grant from Research to Prevent Blindness (RPB) to the Department of Ophthalmology, University of Florida, and grants from the George Gund/National Retinitis Pigmentosa Foundation (J.L., M.I.S., M.L.A., and D.B.F.). M.L.A. is a recipient of the RPB Jules and Doris Stein Professorship. J.G.F. is a recipient of the RPB Research Career Development Award. D.B.F. is a recipient of the RPB Senior Scientific Investigator Award. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Funding AgencyGrant Number
Research to Prevent BlindnessUNSPECIFIED
George Gund/National Retinitis Pigmentosa FoundationUNSPECIFIED
Subject Keywords:retinitis pigmentosa; photoreceptor; phototransduction
Issue or Number:10
PubMed Central ID:PMC49094
Record Number:CaltechAUTHORS:LEMpnas92
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7617
Deposited By: Tony Diaz
Deposited On:14 Mar 2007
Last Modified:08 Nov 2021 20:44

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