Defective Neurogenesis in Citron Kinase Knockout Mice by Altered Cytokinesis and Massive Apoptosis

Neuron. 2000 Oct;28(1):115-27. doi: 10.1016/s0896-6273(00)00090-8.

Abstract

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 vivo its biologic functions, we have inactivated Citron-K gene in mice by homologous recombination. Citron-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 nervous system due to altered cytokinesis and massive apoptosis. Our results indicate that Citron-K is essential for cytokinesis in vivo but only in specific neuronal precursors. Moreover, they suggest a novel molecular mechanism for a subset of human malformative syndromes of the CNS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Ataxia / etiology
  • Brain / embryology
  • Brain / pathology
  • Cell Division / genetics*
  • Cyclin D1 / metabolism
  • DNA / biosynthesis
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Knockout
  • Neurodegenerative Diseases / complications
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / pathology
  • Neurons / metabolism*
  • Neurons / pathology
  • Polyploidy
  • Protein-Serine-Threonine Kinases / biosynthesis
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics*
  • Seizures / etiology
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • rho-Associated Kinases

Substances

  • Intracellular Signaling Peptides and Proteins
  • Cyclin D1
  • DNA
  • citron-kinase
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases