[HTML][HTML] Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice

Y Meng, Y Zhang, V Tregoubov, C Janus, L Cruz… - Neuron, 2002 - cell.com
Y Meng, Y Zhang, V Tregoubov, C Janus, L Cruz, M Jackson, WY Lu, JF MacDonald…
Neuron, 2002cell.com
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 …
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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