A targeted deleterious allele of the splicing factor SCNM1 in the mouse.
Document Type
Article
Publication Date
2008
Keywords
Animals, Blotting-Western, Brain, COS-Cells, Carrier-Proteins, Cell-Nucleus, Cells-Cultured, Cercopithecus-aethiops, Fibroblasts, Gene-Deletion, Gene-Expression-Profiling, Gene-Targeting, Immunoprecipitation, Mice-Inbred-C57BL, Movement-Disorders, Mutation, Myogenic-Regulatory-Factors, Nerve-Tissue-Proteins, Phenotype, Protein-Interaction-Mapping, RNA-Splicing, RNA-Binding-Proteins, Skin, Sodium-Channels, Spliceosomes, Transfection, Two-Hybrid-System-Techniques
First Page
1419
Last Page
1427
JAX Source
Genetics 2008 Nov; 180(3):1419-27.
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.
Recommended Citation
Howell VM,
de HG,
Bergren S,
Jones JM,
Culiat CT,
Michaud EJ,
Frankel WN,
Meisler MH.
A targeted deleterious allele of the splicing factor SCNM1 in the mouse. Genetics 2008 Nov; 180(3):1419-27.