Dataset Information

Phenotypic and genetic analysis of the cerebellar mutant tmgc26, a new ENU-induced ROR-alpha allele.

ABSTRACT: 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.

SUBMITTER: Swanson DJ

PROVIDER: S-EPMC2974799 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Phenotypic and genetic analysis of the cerebellar mutant tmgc26, a new ENU-induced ROR-alpha allele.

Swanson Douglas J DJ Steshina Ekaterina Y EY Wakenight Paul P Aldinger Kimberly A KA Goldowitz Dan D Millen Kathleen J KJ Chizhikov Victor V VV

The European journal of neuroscience 20100816 5

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 ...[more]

PMID: 20722722

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Dataset Information

Phenotypic and genetic analysis of the cerebellar mutant tmgc26, a new ENU-induced ROR-alpha allele.

Publications

Phenotypic and genetic analysis of the cerebellar mutant tmgc26, a new ENU-induced ROR-alpha allele.

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