Restricted Morphological and Behavioral Abnormalities following Ablation of β-Actin in the Brain

Hdl Handle:
http://hdl.handle.net/10675.2/699
Title:
Restricted Morphological and Behavioral Abnormalities following Ablation of β-Actin in the Brain
Authors:
Cheever, Thomas R.; Li, Bin; Ervasti, James M.
Abstract:
The local translation of β-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 β-actin translation in neurons has not yet been demonstrated in vivo. To investigate the role of β-actin in the mammalian central nervous system (CNS), we characterized brain structure and function in a CNS-specific β-actin knock-out mouse (CNS-ActbKO). β-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 β-actin in culture were morphologically normal. Altogether, we identified novel roles for β-actin in promoting complex CNS tissue architecture while also demonstrating that distinct functions for the ubiquitously expressed β-actin are surprisingly restricted in vivo.
Editors:
Mei, Lin
Citation:
PLoS One. 2012 Mar 5; 7(3):e32970
Issue Date:
5-Mar-2012
URI:
http://hdl.handle.net/10675.2/699
DOI:
10.1371/journal.pone.0032970
PubMed ID:
22403730
PubMed Central ID:
PMC3293915
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Neurology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorCheever, Thomas R.en_US
dc.contributor.authorLi, Binen_US
dc.contributor.authorErvasti, James M.en_US
dc.contributor.editorMei, Lin-
dc.date.accessioned2012-10-26T16:29:36Z-
dc.date.available2012-10-26T16:29:36Z-
dc.date.issued2012-03-5en_US
dc.identifier.citationPLoS One. 2012 Mar 5; 7(3):e32970en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid22403730en_US
dc.identifier.doi10.1371/journal.pone.0032970en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/699-
dc.description.abstractThe local translation of β-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 β-actin translation in neurons has not yet been demonstrated in vivo. To investigate the role of β-actin in the mammalian central nervous system (CNS), we characterized brain structure and function in a CNS-specific β-actin knock-out mouse (CNS-ActbKO). β-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 β-actin in culture were morphologically normal. Altogether, we identified novel roles for β-actin in promoting complex CNS tissue architecture while also demonstrating that distinct functions for the ubiquitously expressed β-actin are surprisingly restricted in vivo.en_US
dc.rightsCheever et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectNeurological Systemen_US
dc.subjectHistologyen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectCellular Structuresen_US
dc.subjectCellular Typesen_US
dc.subjectNeuroscienceen_US
dc.subjectCellular Neuroscienceen_US
dc.subjectDevelopmental Neuroscienceen_US
dc.subjectPhysicsen_US
dc.subjectBiophysicsen_US
dc.subjectCell Motilityen_US
dc.subject.meshActinsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBehavior, Animalen_US
dc.subject.meshBrainen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshGene Knockout Techniquesen_US
dc.subject.meshHippocampusen_US
dc.subject.meshMiceen_US
dc.subject.meshNeuronsen_US
dc.subject.meshPhenotypeen_US
dc.titleRestricted Morphological and Behavioral Abnormalities following Ablation of β-Actin in the Brainen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3293915en_US
dc.contributor.corporatenameDepartment of Neurology-
dc.contributor.corporatenameCollege of Graduate Studies-

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