Reproductive Function in Protein Kinase Inhibitor-Deficient Mice

Abstract

The protein kinase inhibitor (PKI) family includes three genes encoding small, heat-stable inhibitors of the cyclic AMP-dependent kinase PKA. Each PKI isoform contains a PKA inhibitory domain and a nuclear export domain, enabling PKI to both inhibit PKA and remove it from the nucleus. The PKIβ isoform, also known as testis PKI, is highly expressed in germ cells of the testis and is found at more modest levels in other tissues. In order to investigate its physiological role, we have generated PKIβ knockout mice by gene targeting. These mice exhibit a partial loss of PKI activity in testis but remain fertile with normal testis development and function. PKIβ knockout females also reproduce normally. The PKIβ mutants were crossed with our previously derived PKIα mutants to obtain double-knockout mice. Remarkably, these mice are also viable and fertile with no obvious physiological defects in either males or females.

ACKNOWLEDGMENTS

Grants from the National Institutes of Health to R.L.I. (HD 33057) and E.A.G. (training grant T32 DK07247) are gratefully acknowledged.

We thank R. Scott Frayo, Michael W. Schnarr, and Taimane L. Sa'Au for valuable technical assistance and Susan Carey and Kathy Kafer for providing essential mouse care and embryo manipulation. We are very grateful to Michael D. Uhler for providing the PKIβ genomic clone.