| First Author | Swanson DJ | Year | 2010 |
| Journal | Eur J Neurosci | Volume | 32 |
| Issue | 5 | Pages | 707-16 |
| PubMed ID | 20722722 | Mgi Jnum | J:171777 |
| Mgi Id | MGI:4999693 | Doi | 10.1111/j.1460-9568.2010.07330.x |
| Citation | Swanson DJ, et al. (2010) Phenotypic and genetic analysis of the cerebellar mutant tmgc26, a new ENU-induced ROR-alpha allele. Eur J Neurosci 32(5):707-16 |
| abstractText | ROR-alpha is an orphan nuclear receptor, inactivation of which cell-autonomously blocks differentiation of cerebellar Purkinje cells with a secondary loss of granule neurons. As part of our ENU mutagenesis screen we isolated the recessive tmgc26 mouse mutant, characterized by early-onset progressive ataxia, cerebellar degeneration and juvenile lethality. Detailed analysis of the tmgc26-/- cerebella revealed Purkinje cell and granule cell abnormalities, and defects in molecular layer interneurons and radial glia. Chimera studies suggested a cell-autonomous effect of the tmgc26 mutation in Purkinje cells and molecular layer interneurons, and a non-cell-autonomous effect in granule cells. The mutation was mapped to a 13-Mb interval on chromosome 9, a region that contains the ROR-alpha gene. Sequencing of genomic DNA revealed a T-to-A transition in exon 5 of the ROR-alpha gene, resulting in a nonsense mutation C257X and severe truncation of the ROR-alpha protein. Together, our data identify new roles for ROR-alpha in molecular layer interneurons and radial glia development and suggest tmgc26 as a novel ROR-alpha allele that may be used to further delineate the molecular mechanisms of ROR-alpha action. |
