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Publication : Calcium/calmodulin kinase kinase beta has a male-specific role in memory formation.

First Author  Mizuno K Year  2007
Journal  Neuroscience Volume  145
Issue  2 Pages  393-402
PubMed ID  17207577 Mgi Jnum  J:121656
Mgi Id  MGI:3710905 Doi  10.1016/j.neuroscience.2006.11.056
Citation  Mizuno K, et al. (2007) Calcium/calmodulin kinase kinase beta has a male-specific role in memory formation. Neuroscience 145(2):393-402
abstractText  The calcium/calmodulin (CaM) kinase cascade regulates gene transcription, which is required for long-term memory formation. Previous studies with Camkk2 null mutant mice have shown that in males calcium/calmodulin kinase kinase beta (CaMKKbeta) is required for spatial memory formation and for activation of the transcription factor cyclic AMP-responsive element binding protein (CREB) in the hippocampus by spatial training. Here we show that CaMKKbeta is not required for spatial memory formation in female mice as female Camkk2 null mutants were not impaired in spatial memory formation and they had the same level of hippocampal CREB phosphorylation after spatial training as female wild-type mice. Furthermore, we show that male but not female Camkk2 null mutants were impaired in long-term potentiation (LTP) at hippocampal CA1 synapses. Finally, a transcriptional analysis of male Camkk2 null mutants led to the identification of a gene, glycosyl phosphatidyl-inositol anchor attachment protein 1 (GAA1), whose hippocampal mRNA expression was up-regulated by spatial and contextual training in male but not in female wild-type mice. Taken together, we conclude that CaMKKbeta has a male-specific function in hippocampal memory formation and we have identified male-restricted transcription occurring during hippocampal memory formation.
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