| First Author | Ha S | Year | 2015 |
| Journal | Cereb Cortex | Volume | 25 |
| Issue | 1 | Pages | 167-79 |
| PubMed ID | 23968836 | Mgi Jnum | J:199782 |
| Mgi Id | MGI:5504641 | Doi | 10.1093/cercor/bht209 |
| Citation | Ha S, et al. (2015) A forward genetic screen in mice identifies mutants with abnormal cortical patterning. Cereb Cortex 25(1):167-79 |
| abstractText | 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. |
