Defective neurogenesis in citron kinase knockout mice by altered cytokinesis and massive apoptosis

Citron-kinase (Citron-K) has been proposed by in vitro studies as a crucial effector of Rho in regulation of cytokinesis. To further investigate in vi vo its biologic functions, we have inactivated Citron-K gene in mice by hom ologous recombination. Cifron-K-/- mice grow at slower rates, are severely ataxic, and die before adulthood as a consequence of fatal seizures. Their brains display defective neurogenesis, with depletion of specific neuronal populations. These abnormalities arise during development of the central ne rvous system due to altered cytokinesis and massive apoptosis. Our results indicate that Citron-K is essential for cytokinesis in vivo but only in spe cific neuronal precursors. Moreover, they suggest a novel molecular mechani sm for a subset of human malformative syndromes of the CNS.