Derangements of hippocampal calcium/calmodulin-dependent protein kinase II in a mouse model for Angelman mental retardation syndrome.
Weeber EJ,
Jiang YH,
Elgersma Y,
Varga AW,
Carrasquillo Y,
Brown SE,
Christian JM,
Mirnikjoo B,
Silva A,
Beaudet AL,
Sweatt JD.
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
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.
PMID: 12684449 [PubMed - indexed for MEDLINE]