Cyclic nucleotides have been implicated in the differentiation and function of the vertebrate retina. In the normal retina of DBA mice, the specific activity of cyclic-nucleotide phosphodiesterase (PDE), with cyclic-AMP as the substrate (cAMP-PDE), increases eightfold between the 6th and 20th postnatal day. Kinetic analysis of retinae from newborn mice reveals a PDE with a single Michaelis constant (Km) value for cyclic-AMP (low Km-PDE). After the 6th postnatal day, a second PDE with a high Km for cyclic-AMP (high Km-PDE) can be demonstrated. The appearance and increasing activity of the high Km-PDE coincides with the differentiation and growth of photoreceptor outer segments. Additionally, the high Km-PDE is shown by microchemical techniques to be concentrated in the photoreceptor cell layer and the low Km-PDE within the inner layers of the normal retina. In C3H mice afflicted with an inherited degeneration of the photoreceptor layer, the postnatal increase in the specific activity of cAMP-PDE is substantially lower than in the normal retina. The postnatal increase in the specific activity of cAMP-PDE in two regions of the brain of C3H mice is the same as in the normal strain. A deficiency in high Km-PDE activity in the C3H retina is evident on the 7th postnatal day, when the activity of low Km-PDE, photoreceptor morphology, and rhodopsin content of these retina are essentially normal. In the adult C3H retina, the PDE activity with cyclic-GMP and cyclic-UMP as substrates is significantly below that of the normal retina. These data indicate that an alteration in cyclic-AMP metabolism occurs before photoreceptor cell degeneration in the retinae of C3H mice.
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1 April 1973
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April 01 1973
CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE : An Early Defect in Inherited Retinal Degeneration of C3H Mice
Susan Y. Schmidt,
Susan Y. Schmidt
From the Department of Anatomy, University of California School of Medicine at Los Angeles, California 90024, and the Developmental Neurology Laboratory, Veterans Administration Hospital, Sepulveda, California 91343
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Richard N. Lolley
Richard N. Lolley
From the Department of Anatomy, University of California School of Medicine at Los Angeles, California 90024, and the Developmental Neurology Laboratory, Veterans Administration Hospital, Sepulveda, California 91343
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Susan Y. Schmidt
From the Department of Anatomy, University of California School of Medicine at Los Angeles, California 90024, and the Developmental Neurology Laboratory, Veterans Administration Hospital, Sepulveda, California 91343
Richard N. Lolley
From the Department of Anatomy, University of California School of Medicine at Los Angeles, California 90024, and the Developmental Neurology Laboratory, Veterans Administration Hospital, Sepulveda, California 91343
Received:
August 31 1972
Revision Received:
November 13 1972
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Copyright © 1973 by The Rockefeller University Press
1973
J Cell Biol (1973) 57 (1): 117–123.
Article history
Received:
August 31 1972
Revision Received:
November 13 1972
Citation
Susan Y. Schmidt, Richard N. Lolley; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE : An Early Defect in Inherited Retinal Degeneration of C3H Mice . J Cell Biol 1 April 1973; 57 (1): 117–123. doi: https://doi.org/10.1083/jcb.57.1.117
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