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PMID: 10518565 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Impaired growth and fertility of cAMP-specific phosphodiesterase PDE4D-deficient mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 21 ·1999-10-12 ·Pages 11998-2003

Jin SL, Richard FJ, Kuo WP, D'Ercole AJ, Conti M

Abstract

In eukaryotic cells, the inactivation of the cyclic nucleotide signal depends on a complex array of cyclic nucleotide phosphodiesterases (PDEs). Although it has been established that multiple PDE isoenzymes with distinct catalytic properties and regulations coexist in the same cell, the physiological significance of this remarkable complexity is poorly understood. To examine the role of a PDE in cAMP signaling in vivo, we have inactivated the type 4 cAMP-specific PDE (PDE4D) gene, a mammalian homologue of the Drosophila dunce. This isoenzyme is involved in feedback regulation of cAMP levels. Mice deficient in PDE4D exhibit delayed growth as well as reduced viability and female fertility. The decrease in fertility of the null female is caused by impaired ovulation and diminished sensitivity of the granulosa cells to gonadotropins. These pleiotropic phenotypes demonstrate that PDE4D plays a critical role in cAMP signaling and that the activity of this isoenzyme is required for the regulation of growth and fertility.

MeSH Terms
3',5'-Cyclic-AMP Phosphodiesterases/genetics,physiology Age Factors Animals Body Weight Exons Female Fertility/genetics Gene Library Granulosa Cells/metabolism Male Mice Mice, Inbred C57BL Models, Genetic Ovulation/metabolism Phenotype Recombination, Genetic Reverse Transcriptase Polymerase Chain Reaction Sex Factors
Chemicals
3',5'-Cyclic-AMP Phosphodiesterases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Jin S L
Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, Stanford, CA 94305-5317, USA.
Richard F J
Kuo W P
D'Ercole A J
Conti M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.21.11998
Published
1999-10-12
Pages
11998-2003
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC18401
Subset
IM
Grants
NICHD NIH HHS · HD20788 · United States
NICHD NIH HHS · HD31544 · United States
NICHD NIH HHS · R01 HD020788 · United States
NICHD NIH HHS · U54-HD31398-02 · United States
NICHD NIH HHS · R01 HD031544 · United States
NICHD NIH HHS · U54 HD031398 · United States
External Links
PubMed source DOI: 10.1073/pnas.96.21.11998 PMC Full Text View journal details
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