Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice |
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Authors: | Meng Yanghong Zhang Yu Tregoubov Vitali Janus Christopher Cruz Luis Jackson Mike Lu Wei Yang MacDonald John F Wang Jay Y Falls Douglas L Jia Zhengping |
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Affiliation: | Program in Brain and Behavior, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. |
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Abstract: | In vitro studies indicate a role for the LIM kinase family in the regulation of cofilin phosphorylation and actin dynamics. In addition, abnormal expression of LIMK-1 is associated with Williams syndrome, a mental disorder with profound deficits in visuospatial cognition. However, the in vivo function of this family of kinases remains elusive. Using LIMK-1 knockout mice, we demonstrate a significant role for LIMK-1 in vivo in regulating cofilin and the actin cytoskeleton. Furthermore, we show that the knockout mice exhibited significant abnormalities in spine morphology and in synaptic function, including enhanced hippocampal long-term potentiation. The knockout mice also showed altered fear responses and spatial learning. These results indicate that LIMK-1 plays a critical role in dendritic spine morphogenesis and brain function. |
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