Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of alphaCaMKII inhibitory phosphorylation.
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 alphaCaMKII. 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 alphaCaMKII.
van Woerden
Geeske M
GM
Erasmus MC, University Medical Centre, Department of Neuroscience, Dr. Molewaterplein 50, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Harris
Karen D
KD
Hojjati
Mohammad Reza
MR
Gustin
Richard M
RM
Qiu
Shenfeng
S
de Avila Freire
Rogerio
R
Jiang
Yong-hui
YH
Elgersma
Ype
Y
Weeber
Edwin J
EJ
D017204:Angelman Syndrome / Q000150:complications* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001522:Behavior, Animal; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D018782:Maze Learning / Q000502:physiology; D001523:Mental Disorders / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009043:Motor Activity / Q000502:physiology; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D011930:Reaction Time; D013997:Time Factors; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
C502429:Ube3a protein, mouse; D044767:Ubiquitin-Protein Ligases; D010770:Phosphotransferases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2