Abstract
Angelman syndrome (AS) is a severe neurological disorder characterized by mental retardation, motor dysfunction and epilepsy. We show that the molecular and cellular deficits of an AS mouse model can be rescued by introducing an additional mutation at the inhibitory phosphorylation site of αCaMKII. Moreover, these double mutants no longer show the behavioral deficits seen in AS mice, suggesting that these deficits are the direct result of increased inhibitory phosphorylation of αCaMKII.
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Change history
06 February 2007
added supplementary methods piece
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Acknowledgements
The authors thank M. Elgersma and M. Aghadavoud Jolfaei for technical support. This work was supported by the Netherlands Organization for Scientific Research (NWO-ZonMW), Hersenstichting Nederland (HsN), Netherlands Epilepsy Fund and the Nina Foundation/Angelman Vereniging.
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Supplementary information
Supplementary Fig. 1
Decreased inhibitory phosphorylation in hippocampal lysates of AS/CaMKII-305/6+/− double mutants. (PDF 594 kb)
Supplementary Fig. 2
The increased bodyweight in AS mice returns to WT level in AS/CaMKII-305/6+/− mice. (PDF 18 kb)
Supplementary Fig. 3
Learning of the hidden platform (a-e) and visible (f) platform water maze. (PDF 330 kb)
Supplementary Fig. 4
AS mice show no deficits in cued conditioning. (PDF 16 kb)
Supplementary Methods
(PDF 147 kb)
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van Woerden, G., Harris, K., Hojjati, M. et al. Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of αCaMKII inhibitory phosphorylation. Nat Neurosci 10, 280–282 (2007). https://doi.org/10.1038/nn1845
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DOI: https://doi.org/10.1038/nn1845
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