Impaired growth and fertility of cAMP-specific phosphodiesterase PDE4D-deficient mice
Impaired growth and fertility of cAMP-specific phosphodiesterase PDE4D-deficient mice
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DOI：
10.1073/pnas.96.21.11998
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发表时间：
1999-10-12
影响因子：
11.1
通讯作者：
Conti, M
中科院分区：
文献类型：
--
作者：
Jin, SLC;Richard, FJ;Conti, M
在真核细胞中，环核苷酸信号的失活取决于环核苷酸磷酸二酯酶（PDE）的复杂阵列。虽然它已经建立了多个PDE同工酶具有不同的催化性能和法规共存于同一个细胞，这种显着的复杂性的生理意义知之甚少。为了研究PDE在体内cAMP信号传导中的作用，我们已经灭活了4型cAMP特异性PDE（PDE4D）基因，这是果蝇的哺乳动物同源物。这种同工酶参与cAMP水平的反馈调节。PDE4D缺陷小鼠表现出生长延迟以及活力和雌性生育力降低。无效雌性的生育力下降是由排卵障碍和颗粒细胞对促性腺激素敏感性降低引起的。这些多效性表型表明，PDE 4D在cAMP信号传导中起关键作用，并且该同工酶的活性是调节生长和生育力所必需的。
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.