Referenced in: none

Automatically associated channels: Nav1.6

Title: A targeted deleterious allele of the splicing factor SCNM1 in the mouse.

Authors: Viive M Howell, Georgius de Haan, Sarah Bergren, Julie M Jones, Cymbeline T Culiat, Edward J Michaud, Wayne N Frankel, Miriam H Meisler

Journal, date & volume: Genetics, 2008 Nov , 180, 1419-27

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18791226

Abstract
The auxiliary spliceosomal protein SCNM1 contributes to recognition of nonconsensus splice donor sites. SCNM1 was first identified as a modifier of the severity of a sodium channelopathy in the mouse. The most severely affected strain, C57BL/6J, carries the variant allele SCNM1R187X, which is defective in splicing the mutated donor site in the Scn8a(medJ) transcript. To further probe the in vivo function of SCNM1, we constructed a floxed allele and generated a mouse with constitutive deletion of exons 3-5. The SCNM1Delta3-5 protein is produced and correctly localized to the nucleus, but is more functionally impaired than the C57BL/6J allele. Deficiency of SCNM1 did not significantly alter other brain transcripts. We characterized an ENU-induced allele of Scnm1 and evaluated the ability of wild-type SCNM1 to rescue lethal mutations of I-mfa and Brunol4. The phenotypes of the Scnm1Delta3-5 mutant confirm the role of this splice factor in processing the Scn8a(medJ) transcript and provide a new allele of greater severity for future studies.