Journal article
Mutations in α-Tubulin Cause Abnormal Neuronal Migration in Mice and Lissencephaly in Humans
Cell, Vol.128(1), pp.45-57
2007
Abstract
The development of the mammalian brain is dependent on extensive neuronal migration. Mutations in mice and humans that affect neuronal migration result in abnormal lamination of brain structures with associated behavioral deficits. Here, we report the identification of a hyperactive N-ethyl-N-nitrosourea (ENU)-induced mouse mutant with abnormalities in the laminar architecture of the hippocampus and cortex, accompanied by impaired neuronal migration. We show that the causative mutation lies in the guanosine triphosphate (GTP) binding pocket of α-1 tubulin (Tuba1) and affects tubulin heterodimer formation. Phenotypic similarity with existing mouse models of lissencephaly led us to screen a cohort of patients with developmental brain anomalies. We identified two patients with de novo mutations in TUBA3, the human homolog of Tuba1. This study demonstrates the utility of ENU mutagenesis in the mouse as a means to discover the basis of human neurodevelopmental disorders. © 2007 Elsevier Inc. All rights reserved.
Details
- Title
- Mutations in α-Tubulin Cause Abnormal Neuronal Migration in Mice and Lissencephaly in Humans
- Authors
- D A Keays (Author) - University of Oxford, United KingdomG Tian (Author) - New York University Medical Center, United StatesK Poirier (Author) - Université René Descartes, FranceG J Huang (Author) - University of Oxford, United KingdomC Siebold (Author) - University of Oxford, United KingdomJ Cleak (Author) - University of Oxford, United KingdomP L Oliver (Author) - MRC Functional Genetics Unit, United KingdomM Fray (Author) - MRC Mammalian Genetics Unit, United KingdomRobert J Harvey (Author) - University College London, United KingdomZ Molnár (Author) - University of Oxford, United KingdomM C Piñon (Author) - University of Oxford, United KingdomN Dear (Author) - MRC Mammalian Genetics Unit, United KingdomW Valdar (Author) - University of Oxford, United KingdomS D M Brown (Author) - MRC Mammalian Genetics Unit, United KingdomK E Davies (Author) - MRC Functional Genetics Unit, United KingdomJ N P Rawlins (Author) - University of Oxford, United KingdomN J Cowan (Author) - New York University Medical Center, United StatesP Nolan (Author) - MRC Mammalian Genetics Unit, United KingdomJ Chelly (Author) - Université René Descartes, FranceJ Flint (Author) - University of Oxford, United Kingdom
- Publication details
- Cell, Vol.128(1), pp.45-57
- Publisher
- Cell Press
- Date published
- 2007
- DOI
- 10.1016/j.cell.2006.12.017
- ISSN
- 0092-8674
- Copyright note
- Copyright © Keays, D A et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 License.
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99450596902621
- Output Type
- Journal article
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