| First Author | Sachs AJ | Year | 2007 |
| Journal | Mamm Genome | Volume | 18 |
| Issue | 11 | Pages | 749-56 |
| PubMed ID | 17934773 | Mgi Jnum | J:127311 |
| Mgi Id | MGI:3763560 | Doi | 10.1007/s00335-007-9064-y |
| Citation | Sachs AJ, et al. (2007) The mouse mutants recoil wobbler and nmf373 represent a series of Grm1 mutations. Mamm Genome 18(11):749-56 |
| abstractText | The identification of novel mutant alleles is important for understanding critical functional domains of a protein and establishing genotype:phenotype correlations. The recoil wobbler (rcw) allelic series of spontaneous ataxic mutants and the ENU-induced mutant nmf373 genetically mapped to a shared region of chromosome 10. Their mutant phenotypes are strikingly similar; all have an ataxic phenotype that is recessive, early-onset, and is not associated with neurodegeneration. In this study we used complementation tests to show that these series of mutants are allelic to a knockout mutant of Grm1. Subsequently, a duplication of exon 4 and three missense mutations were identified in Grm1: I160T, E292D, and G337E. All mutations occurred within the ligand-binding region and changed conserved amino acids. In the rcw mutant, the Grm1 gene is expressed and the protein product is properly localized to the molecular layer of the cerebellar cortex. Grm1 is responsible for the generation of inositol 1,4,5-trisphosphate (IP(3)). The inositol second messenger system is the central mechanism for calcium release from intracellular stores in cerebellar Purkinje cells. Several of the genes involved in this pathway are mutated in mouse ataxic disorders. The novel rcw mutants represent a resource that will have utility for further studies of inositol second-messenger-system defects in neurogenetic disorders. |
