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J. Neurosci. 23 (7): 2634-2644

Copyright © 2003 by the Society for Neuroscience.

The Journal of Neuroscience, April 1, 2003, 23(7):2634

Derangements of Hippocampal Calcium/Calmodulin-Dependent Protein Kinase II in a Mouse Model for Angelman Mental Retardation Syndrome

Edwin J. Weeber1, Yong-Hui Jiang2, Ype Elgersma3, 4, Andrew W. Varga1, Yarimar Carrasquillo1, Sarah E. Brown1, Jill M. Christian1, Banefsheh Mirnikjoo1, Alcino Silva3, Arthur L. Beaudet2, and J. David Sweatt1

1 Division of Neuroscience and 2 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, 3 Department of Neurobiology, University of California, Los Angeles, Medical Center, Los Angeles, California 90095-1763, and 4 Department of Neuroscience, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands

Angelman syndrome (AS) is a disorder of human cognition characterized by severe mental retardation and epilepsy. Recently, a mouse model for AS (Ube3a maternal null mutation) was developed that displays deficits in both context-dependent learning and hippocampal long-term potentiation (LTP). In the present studies, we examined the molecular basis for these LTP and learning deficits. Mutant animals exhibited a significant increase in hippocampal phospho-calcium/calmodulin-dependent protein kinase II (CaMKII), specifically at sites Thr286 and Thr305, with no corresponding change in the levels of total CaMKII. In addition, mutants show a reduction in CaMKII activity, autophosphorylation capability, and total CaMKII associated with postsynaptic density. These findings are the first to implicate misregulation of CaMKII as a molecular cause for the neurobehavioral deficits in a human learning disorder.

Key words: Angelman syndrome; calcium/calmodulin-dependent protein kinase II; long-term potentiation; postsynaptic density; protein phosphatase; autophosphorylation

Copyright © 2003 Society for Neuroscience  0270-6474/03/2372634-11$05.00/0

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