title: Abnormalities in brain structure and behavior in GSK-3alpha mutant mice.
abstract: 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-3alpha and GSK-3beta. Mice lacking a functional GSK-3alpha gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3alpha 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-3beta(+/-) mice, GSK-3alpha mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3alpha 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-3alpha 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.
  
  
  CONCLUSIONS
  Taken together, these data support a role for the GSK-3alpha gene in CNS functioning and possible involvement in the development of psychiatric disorders.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada. beilin@lunenfeld.ca
authors.forename: Oksana
authors.initials: O
authors.lastname: Kaidanovich-Beilin
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Lipina
authors.forename: Keizo
authors.initials: K
authors.lastname: Takao
authors.forename: Matthijs
authors.initials: M
authors.lastname: van Eede
authors.forename: Satoko
authors.initials: S
authors.lastname: Hattori
authors.forename: Christine
authors.initials: C
authors.lastname: Laliberté
authors.forename: Mustafa
authors.initials: M
authors.lastname: Khan
authors.forename: Kenichi
authors.initials: K
authors.lastname: Okamoto
authors.forename: John W
authors.initials: JW
authors.lastname: Chambers
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fletcher
authors.forename: Katrina
authors.initials: K
authors.lastname: MacAulay
authors.forename: Bradley W
authors.initials: BW
authors.lastname: Doble
authors.forename: Mark
authors.initials: M
authors.lastname: Henkelman
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.forename: John
authors.initials: J
authors.lastname: Roder
authors.forename: James R
authors.initials: JR
authors.lastname: Woodgett
mesh_terms: D000374:Aggression / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000002:abnormalities* / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D003863:Depression / Q000473:pathology / Q000503:physiopathology; D004644:Emotions; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000172:deficiency / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D057567:Memory, Long-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D018377:Neurotransmitter Agents / Q000378:metabolism; D012919:Social Behavior
chemical_list: D018377:Neurotransmitter Agents; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha