Abnormalities in brain structure and behavior in GSK-3alpha mutant mice

Oksana Kaidanovich-Beilin, Tatiana V. Lipina, Keizo Takao, Matthijs Van Eede, Satoko Hattori, Christine Laliberté, Mustafa Khan, Kenichi Okamoto, John W. Chambers, Paul J. Fletcher, Katrina MacAulay, Bradley W. Doble, Mark Henkelman, Tsuyoshi Miyakawa, John Roder, James R. Woodgett

Research output: Contribution to journalArticlepeer-review

139 Citations (Scopus)


Background. Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by two genes that generate two related proteins: GSK-3 and GSK-3. Mice lacking a functional GSK-3 gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3 KO mice by using a well-established battery of behavioral tests together with neurochemical and neuroanatomical analysis. Results. Similar to the previously described behaviours of GSK-3+/-mice, GSK-3 mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3 gene was associated with: decreased locomotion and impaired motor coordination, increased grooming activity, loss of social motivation and novelty; enhanced sensorimotor gating and impaired associated memory and coordination. GSK-3 KO mice exhibited a deficit in fear conditioning, however memory formation as assessed by a passive avoidance test was normal, suggesting that the animals are sensitized for active avoidance of a highly aversive stimulus in the fear-conditioning paradigm. Changes in cerebellar structure and function were observed in mutant mice along with a significant decrease of the number and size of Purkinje cells. Conclusion. Taken together, these data support a role for the GSK-3 gene in CNS functioning and possible involvement in the development of psychiatric disorders.

Original languageEnglish
Article number35
JournalMolecular brain
Issue number1
Publication statusPublished - 2009

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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