Targeted Disruption of the Gene for the PAK5 Kinase in Mice

Abstract

PAK5 is a member of the group B family of PAK serine/threonine kinases and is an effector for the Rho GTPase Cdc42. PAK5 is highly expressed in the brain and is expressed at lower levels in several other tissues. In cell lines, PAK5 has been shown to play a role in filopodia formation and neurite outgrowth. To examine the biological function of PAK5, we deleted the PAK5 gene in mice. The phenotypes of the PAK5-null mice are completely different from those of mice null for PAK4, another member of the group B PAK family. Unlike PAK4-null mice, which are embryonic lethal, PAK5-null mice develop normally and are fertile. The nervous system appears normal in the absence of PAK5, as do other tissues in which PAK5 is normally expressed. Our results suggest functional redundancy between PAK5 and other Rho GTPase targets.

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Targeted Disruption of the Gene for the PAK5 Kinase in Mice

ACKNOWLEDGMENTS

We thank C. Yang of Rockefeller University for help with the ES cell culture and injection, A. Beg for providing the S129 genomic library, R. G. Russell for helping with the histology analysis, and J. Qu for help in developing the knockouts.

This work was supported by NIH grant CA76342 to A.M.