title: A targeted deleterious allele of the splicing factor SCNM1 in the mouse.
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.
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109-5618, USA.
authors.forename: Viive M
authors.initials: VM
authors.lastname: Howell
authors.forename: Georgius
authors.initials: G
authors.lastname: de Haan
authors.forename: Sarah
authors.initials: S
authors.lastname: Bergren
authors.forename: Julie M
authors.initials: JM
authors.lastname: Jones
authors.forename: Cymbeline T
authors.initials: CT
authors.lastname: Culiat
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Michaud
authors.forename: Wayne N
authors.initials: WN
authors.lastname: Frankel
authors.forename: Miriam H
authors.initials: MH
authors.lastname: Meisler
mesh_terms: D000483:Alleles; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D000067878:CELF Proteins; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D018390:Gene Targeting; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009069:Movement Disorders / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D025941:Protein Interaction Mapping; D012326:RNA Splicing / Q000235:genetics*; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D000067878:CELF Proteins; D002352:Carrier Proteins; C470022:Celf4 protein, mouse; C491077:Mdfi protein, mouse; D018006:Myogenic Regulatory Factors; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C491046:Scn8a protein, mouse; C476996:Scnm1 protein, mouse; D015222:Sodium Channels
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