| First Author | Buchner DA | Year | 2003 |
| Journal | Science | Volume | 301 |
| Issue | 5635 | Pages | 967-9 |
| PubMed ID | 12920299 | Mgi Jnum | J:84898 |
| Mgi Id | MGI:2670553 | Doi | 10.1126/science.1086187 |
| Citation | Buchner DA, et al. (2003) SCNM1, a putative RNA splicing factor that modifies disease severity in mice. Science 301(5635):967-9 |
| abstractText | The severity of many inherited disorders is influenced by genetic background. We describe a modifier interaction in C57BL/6Jmice that converts a chronic movement disorder into a lethal neurological disease. The primary mutation (medJ) changes a splice donor site of the sodium channel gene Scn8a (Nav1.6). The modifier mutation is characteristic of strain C57BL/6Jand introduces a nonsense codon into sodium channel modifier 1 (SCNM1), a zinc finger protein and a putative splice factor. An internally deleted SCNM1 protein is also predicted as a result of exon skipping associated with disruption of a consensus exonic splicing enhancer. The effect of the modifier mutation is to reduce the abundance of correctly spliced sodium channel transcripts below the threshold for survival. Our finding that genetic variation in a putative RNA splicing factor influences disease susceptibility in mice raises the possibility that a similar mechanism modifies the severity of human inherited disorders. |
