A Targeted Deleterious Allele of the Splicing Factor SCNM1 in the Mouse
Copyright policy )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 Scn8amedJ 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 SCNM1Δ3-5 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 Scnm1Δ3-5 mutant confirm the role of this splice factor in processing the Scn8amedJ transcript and provide a new allele of greater severity for future studies.
- University of Michigan–Flint United States
- Oak Ridge National Laboratory United States
- Jackson Laboratory United States
- University of Michigan–Ann Arbor United States
Male, 570, Gene-Expression-Profiling, Blotting, Western, RNA-Binding-Proteins, 610, COS-Cells, Nerve-Tissue-Proteins, Transfection, Blotting-Western, Mice, Cercopithecus-aethiops, Gene-Targeting, Chlorocebus aethiops, Animals, CELF Proteins, Immunoprecipitation, Cell-Nucleus, Alleles, Cells, Cultured, Skin, Cell Nucleus, Sodium-Channels, Movement Disorders, Gene Expression Profiling, Mice-Inbred-C57BL, Brain, Fibroblasts, Two-Hybrid-System-Techniques, Mice, Inbred C57BL, Phenotype, Protein-Interaction-Mapping, Cells-Cultured, Mutation, COS Cells, Gene Targeting, Spliceosomes, Carrier-Proteins, RNA-Splicing, Myogenic-Regulatory-Factors, Female, Gene-Deletion, Movement-Disorders, Carrier Proteins, Gene Deletion
Male, 570, Gene-Expression-Profiling, Blotting, Western, RNA-Binding-Proteins, 610, COS-Cells, Nerve-Tissue-Proteins, Transfection, Blotting-Western, Mice, Cercopithecus-aethiops, Gene-Targeting, Chlorocebus aethiops, Animals, CELF Proteins, Immunoprecipitation, Cell-Nucleus, Alleles, Cells, Cultured, Skin, Cell Nucleus, Sodium-Channels, Movement Disorders, Gene Expression Profiling, Mice-Inbred-C57BL, Brain, Fibroblasts, Two-Hybrid-System-Techniques, Mice, Inbred C57BL, Phenotype, Protein-Interaction-Mapping, Cells-Cultured, Mutation, COS Cells, Gene Targeting, Spliceosomes, Carrier-Proteins, RNA-Splicing, Myogenic-Regulatory-Factors, Female, Gene-Deletion, Movement-Disorders, Carrier Proteins, Gene Deletion
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