A Targeted Deleterious Allele of the Splicing Factor SCNM1 in the Mouse

作者：Howell Viive M; de Haan Georgius; Bergren Sarah; Jones Julie M; Culiat Cymbeline T; Michaud Edward J; Frankel Wayne N; Meisler Miriam H^*

来源：Genetics, 2008, 180(3): 1419-1427.

DOI：10.1534/genetics.108.094227

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 SCNM1(R187X), 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 SCNM1(Delta 3-5) 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 Scmn1 and evaluated the ability of wild-type SCNM1 to rescue lethal mutations of I-mfa and Brunol4. The phenotypes of the Scnm1(Delta 3-5) 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.

• 出版日期2008-11