Generation and characterization of Rac3 knockout mice

Mol Cell Biol. 2005 Jul;25(13):5763-76. doi: 10.1128/MCB.25.13.5763-5776.2005.

Abstract

Rac proteins are members of the Rho family of GTPases involved in the regulation of actin dynamics. The three highly homologous Rac proteins in mammals are the ubiquitous Rac1, the hematopoiesis-specific Rac2, and the least-characterized Rac3. We show here that Rac3 mRNA is widely and specifically expressed in the developing nervous system, with highest concentration at embryonic day 13 in the dorsal root ganglia and ventral spinal cord. At postnatal day 7 Rac3 appears particularly abundant in populations of projection neurons in several regions of the brain, including the fifth layer of the cortex and the CA1-CA3 region of the hippocampus. We generated mice deleted for the Rac3 gene with the aim of analyzing the function of this GTPase in vivo. Rac3 knockout animals survive embryogenesis and show no obvious developmental defects. Interestingly, specific behavioral differences were detected in the Rac3-deficient animals, since motor coordination and motor learning on the rotarod was superior to that of their wild-type littermates. No obvious histological or immunohistological differences were observed at major sites of Rac3 expression. Our results indicate that, in vivo, Rac3 activity is not strictly required for normal development in utero but may be relevant to later events in the development of a functional nervous system.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Behavior, Animal
  • Brain Chemistry
  • DNA, Complementary
  • Electroporation
  • Embryo, Mammalian
  • Gene Expression
  • Gene Targeting
  • Genetic Vectors
  • Genome
  • Immunohistochemistry
  • In Situ Hybridization
  • Learning
  • Mice
  • Mice, Knockout
  • Motor Activity / genetics
  • Motor Activity / physiology
  • Precipitin Tests
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • beta-Galactosidase / genetics
  • rac GTP-Binding Proteins / deficiency
  • rac GTP-Binding Proteins / genetics*
  • rac GTP-Binding Proteins / metabolism*

Substances

  • Antibodies, Monoclonal
  • DNA, Complementary
  • RNA, Messenger
  • beta-Galactosidase
  • Rac3 protein, mouse
  • rac GTP-Binding Proteins