• PMID: 11875122
• Gene Name: PRKCA
• Condition: Spermatogenesis progressed normally but that mature sperm had defective forward motility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Spermatogenesis progressed normally but that mature sperm had defective forward motility

Mutation of the Calpha subunit of PKA leads to growth retardation and sperm dysfunction

Skålhegg BS, Huang Y, Su T, Idzerda RL, McKnight GS, Burton KA.

The intracellular second messenger cAMP affects cell physiology by directly interacting with effector molecules that include cyclic nucleotide-gated ion channels, cAMP-regulated G protein exchange factors, and cAMP-dependent protein kinases (PKA). Two catalytic subunits, Calpha and Cbeta, are expressed in the mouse and mediate the effects of PKA. We generated a null mutation in the major catalytic subunit of PKA, Calpha, and observed early postnatal lethality in the majority of Calpha knockout mice. Surprisingly, a small percentage of Calpha knockout mice, although runted, survived to adulthood. This growth retardation was not due to decreased GH production but did correlate with a reduction in IGF-I mRNA in the liver and diminished production of the major urinary proteins in kidney. The survival of Calpha knockout mice after birth is dependent on the genetic background as well as environmental factors, but sufficient adult animals were obtained to characterize the mutants. In these animals, compensatory increases in Cbeta levels occurred in brain whereas many tissues, including skeletal muscle, heart, and sperm, contained less than 10% of the normal PKA activity. Analysis of sperm in Calpha knockout males revealed that spermatogenesis progressed normally but that mature sperm had defective forward motility. FAU - Skålhegg, Bjørn S AU - Skålhegg BS AD - Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195-7750, USA. FAU - Huang, Yongzhao AU - Huang Y FAU - Su, Thomas AU - Su T FAU - Idzerda, Rejean L AU - Idzerda RL FAU - McKnight, G Stanley AU - McKnight GS