Restricted Morphological and Behavioral Abnormalities following Ablation of Î²-Actin in the Brain
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AbstractThe local translation of Î²-actin is one mechanism proposed to regulate spatially-restricted actin polymerization crucial for nearly all aspects of neuronal development and function. However, the physiological significance of localized Î²-actin translation in neurons has not yet been demonstrated in vivo. To investigate the role of Î²-actin in the mammalian central nervous system (CNS), we characterized brain structure and function in a CNS-specific Î²-actin knock-out mouse (CNS-ActbKO). Î²-actin was rapidly ablated in the embryonic mouse brain, but total actin levels were maintained through upregulation of other actin isoforms during development. CNS-ActbKO mice exhibited partial perinatal lethality while survivors presented with surprisingly restricted histological abnormalities localized to the hippocampus and cerebellum. These tissue morphology defects correlated with profound hyperactivity as well as cognitive and maternal behavior impairments. Finally, we also identified localized defects in axonal crossing of the corpus callosum in CNS-ActbKO mice. These restricted defects occurred despite the fact that primary neurons lacking Î²-actin in culture were morphologically normal. Altogether, we identified novel roles for Î²-actin in promoting complex CNS tissue architecture while also demonstrating that distinct functions for the ubiquitously expressed Î²-actin are surprisingly restricted in vivo.
CitationPLoS One. 2012 Mar 5; 7(3):e32970
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