Targeted disruption of the Pak5 and Pak6 genes in mice leads to deficits in learning and locomotion

Tanya Nekrasova, Michelle L. Jobes, Jenhao H. Ting, George C. Wagner, Audrey Minden

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

PAK6 is a member of the group B family of PAK serine/threonine kinases, and is highly expressed in the brain. The group B PAKs, including PAK4, PAK5, and PAK6, were first identified as effector proteins for the Rho GTPase Cdc42. They have important roles in filopodia formation, the extension of neurons, and cell survival. Pak4 knockout mice die in utero, and the embryos have several abnormalities, including a defect in the development of motor neurons. In contrast, Pak5 knockout mice do not have any noticeable abnormalities. So far nothing is known about the biological function of Pak6. To address this, we have deleted the Pak6 gene in mice. Since Pak6 and Pak5 are both expressed in the brain, we also generated Pak5/Pak6 double knockout mice. These mice were viable and fertile, but had several locomotor and behavioral deficits. Our results indicate that Pak5 and Pak6 together are not required for viability, but are required for a normal level of locomotion and activity as well as for learning and memory. This is consistent with a role for the group B PAKs in the nervous system.

Original languageEnglish (US)
Pages (from-to)95-108
Number of pages14
JournalDevelopmental Biology
Volume322
Issue number1
DOIs
StatePublished - Oct 1 2008

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Keywords

  • Cognitive function
  • Elevated maze test
  • Hanging wire test
  • Knockout mice
  • Motor neurons
  • Open field test
  • Pak5
  • Pak6
  • Rotorod test
  • T-maze

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