Derangements of hippocampal calcium/calmodulin-dependent protein kinase II in a mouse model for Angelman mental retardation syndrome.


Journal Article

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.

Full Text

Cited Authors

  • Weeber, EJ; Jiang, Y-H; Elgersma, Y; Varga, AW; Carrasquillo, Y; Brown, SE; Christian, JM; Mirnikjoo, B; Silva, A; Beaudet, AL; Sweatt, JD

Published Date

  • April 2003

Published In

Volume / Issue

  • 23 / 7

Start / End Page

  • 2634 - 2644

PubMed ID

  • 12684449

Pubmed Central ID

  • 12684449

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.23-07-02634.2003


  • eng