Ha, S., Stottmann, R. W., Furley, A. J. orcid.org/0000-0001-5549-8668 et al. (1 more author) (2015) A Forward Genetic Screen in Mice Identifies Mutants with Abnormal Cortical Patterning. Cerebral Cortex, 25 (1). pp. 167-179. ISSN 1047-3211
Abstract
Formation of a 6-layered cortical plate and axon tract patterning are key features of cerebral cortex development. Abnormalities of these processes may be the underlying cause for a range of functional disabilities seen in human neurodevelopmental disorders. To identify mouse mutants with defects in cortical lamination or corticofugal axon guidance, N-ethyl-N-nitrosourea (ENU) mutagenesis was performed using mice expressing LacZ reporter genes in layers II/III and V of the cortex (Rgs4-lacZ) or in corticofugal axons (TAG1-tau-lacZ). Four lines with abnormal cortical lamination have been identified. One of these was a splice site mutation in reelin (Reln) that results in a premature stop codon and the truncation of the C-terminal region (CTR) domain of reelin. Interestingly, this novel allele of Reln did not display cerebellar malformation or ataxia, and this is the first report of a Reln mutant without a cerebellar defect. Four lines with abnormal cortical axon development were also identified, one of which was found by whole-genome resequencing to carry a mutation in Lrp2. These findings demonstrated that the application of ENU mutagenesis to mice carrying transgenic reporters marking cortical anatomy is a sensitive and specific method to identify mutations that disrupt patterning of the developing brain.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © The Author 2013. Published by Oxford University Press. This is an author produced version of a paper subsequently published in Cerebral Cortex. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | cerebral cortex; cortical lamination; corticofugal axon; ENU mutagenesis; reelin |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 27 Mar 2017 13:36 |
Last Modified: | 24 Mar 2018 14:35 |
Published Version: | http://dx.doi.org/10.1093/cercor/bht209 |
Status: | Published |
Publisher: | Oxford University Press (OUP): Policy B - Oxford Open Option B |
Refereed: | Yes |
Identification Number: | 10.1093/cercor/bht209 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:113968 |