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Guanylyl Cyclase Genes and Their Role in Retinal Degeneration

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Retinal Degenerative Diseases and Experimental Therapy

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Abstract

Guanylyl cyclases play a fundamental role in a wide variety of cellular processes. In response to specific regulatory signals these enzymes form the intracellular second messenger molecule cGMP. In vertebrate retinal photoreceptor cells cGMP has been identified as the primary internal messenger for visual transduction more than a decade ago. Inherited defects in cGMP metabolism have been linked to retinal degeneration and blindness even longer. Recently, specific gene defects in one of the retinal isoforms of guanylyl cyclase, RETGC-1, have been found to cause Leber’s congenital amaurosis (LCA) and an autosomal-dominant form of cone-rod dystrophy. We investigated the functional consequences of a RETGC-1 missense mutation (F589S) described in LCA patients. We demonstrate that this mutation markedly decreases enzyme activity when expressed in vitro. Function and possible linkage to eye disease of an X-chromosomal gene encoding a second retinal isoform, RETGC-2, are less clear. We determined the genomic structure of RETGC-2 as a prerequisite for future mutation screening studies.

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Authors and Affiliations

  1. Department of Cell and Neurobiology, University of Southern California School of Medicine, 1333 San Pablo Street BMT 401, Los Angeles, CA, 90033

    Dr. Hans-Jürgen Fülle & Rima Khankan

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  1. Dr. Hans-Jürgen Fülle
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  2. Rima Khankan
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Correspondence to Hans-Jürgen Fülle .

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Editors and Affiliations

  1. Cole Eye Institute, The Cleveland Clinic Foundation, Cleveland, Ohio

    Joe G. Hollyfield

  2. Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma

    Robert E. Anderson

  3. Beckman Vision Center, University of California, San Francisco, San Francisco, California

    Matthew M. LaVail

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© 1999 Kluwer Academic / Plenum Publishers

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Fülle, HJ., Khankan, R. (1999). Guanylyl Cyclase Genes and Their Role in Retinal Degeneration. In: Hollyfield, J.G., Anderson, R.E., LaVail, M.M. (eds) Retinal Degenerative Diseases and Experimental Therapy. Springer, Boston, MA. https://doi.org/10.1007/978-0-585-33172-0_6

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  • DOI: https://doi.org/10.1007/978-0-585-33172-0_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-46193-4

  • Online ISBN: 978-0-585-33172-0

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