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

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...

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Bibliographic Details
Published in:The Journal of neuroscience 2003-04, Vol.23 (7), p.2634-2644
Main Authors: Weeber, Edwin J, Jiang, Yong-Hui, Elgersma, Ype, Varga, Andrew W, Carrasquillo, Yarimar, Brown, Sarah E, Christian, Jill M, Mirnikjoo, Banefsheh, Silva, Alcino, Beaudet, Arthur L, Sweatt, J. David
Format: Article
Language:English
Subjects:
Angelman syndrom
Angelman Syndrome - enzymology
Angelman Syndrome - etiology
Angelman Syndrome - physiopathology
Animals
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - chemistry
Calcium-Calmodulin-Dependent Protein Kinases - immunology
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cells, Cultured
Hippocampus - enzymology
Hippocampus - physiology
Immunohistochemistry
Intellectual Disability - enzymology
Intellectual Disability - etiology
Intellectual Disability - physiopathology
Ligases - genetics
Long-Term Potentiation
Mice
Mutation
Phosphoprotein Phosphatases - metabolism
Phosphorylation
Protein Kinases - metabolism
Synapses - enzymology
Threonine - metabolism
Ubiquitin-Protein Ligases
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Summary: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 Thr(286) and Thr(305), 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.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.23-07-02634.2003