Abnormalities in brain structure and behavior in GSK-3 mutant mice
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, our data support a role for the GSK-3alpha gene in CNS functioning and possible involvement in the development of psychiatric disorders.
Author: Oksana Kaidanovich-BeilinTatiana LipinaKeizo TakaoMatthijs van EedeSatoko HattoriChristine LaliberteMustafa KhanKenichi OkamotoJohn ChambersPaul FletcherKatrina MacAulayBradley DobleMark HenkelmanTsuyoshi MiyakawaJohn RoderJames Woodgett
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Published on: 2009-11-19
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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