A Targeted Deleterious Allele of the Splicing Factor SCNM1 in the Mouse
Open accessAbstract
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.
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Targeted deletion of Scnm1 in the C3H strain confirmed that SCNM1 affects both the splicing of the Scn8amedJ transcript and the mouse phenotype.
“targeted deletion of Scnm1 in the C3H strain confirmed that SCNM1 affects both the splicing of the Scn8amedJ transcript and the mouse phenotype152,153.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [153]
The phenotypic severity of the Scn8amedJ hypomorphic allele is determined by a single gene modifier, Scnm1.
“The phenotypic severity of the Scn8amedJ hypomorphic allele is determined by a single gene modifier, sodium channel modifier 1 (Scnm1).”
From The neurogenetics of alternative splicing (2016) · cites this paper as [153]
SCNM1 overexpression in heterologous cells can enhance the correct splicing of an Scn8a mini-gene.
“Its overexpression in heterologous cells can enhance the correct splicing of an Scn8a mini-gene”
From The neurogenetics of alternative splicing (2016) · cites this paper as [153]
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The neurogenetics of alternative splicing
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- Authors
- Howell, V. M., de Haan, G., Bergren, S., Jones, J. M., Culiat, C. T., Michaud, E. J., Frankel, W. N., & Meisler, M. H.
- Affiliations
- University of Michigan (US)
- Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109-5618
- Oak Ridge National Laboratory (US)
- Jackson Laboratory (US)
- Corresponding author
- Meisler, Miriam H
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-11-01
- Volume
- 180
- Issue
- 3
- Pages
- 1419-1427
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- PMC
- PMC2581945
- OpenAlex
- W2149622625
- Cited by
- 8
- References
- 32
- Citations by year
- 2022: 1 · 2021: 1 · 2016: 1 · 2014: 1 · 2012: 1
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (5P30 CA 46592, P30CA046592)
- National Institute of General Medical Sciences (R01GM024872, R01-GM24872, R24GM070857)
- National Institute of Neurological Disorders and Stroke (R01NS31348, R01NS031348)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- spliceosome, SCN8A, sodium channelopathy, C57BL/6J mice, floxed allele, exon deletion, ENU-induced mutation
- MeSH terms
- CELF Proteins, RNA Splicing Factors, Alleles, Animals, Brain, Carrier Proteins, Cell Nucleus, Cells, Cultured, Chlorocebus aethiops, Female, Fibroblasts, Male, Mice, Inbred C57BL, Movement Disorders, Mutation, Nerve Tissue Proteins, Phenotype, RNA Splicing, Skin, Transfection, Blotting, Western, Sodium Channels, RNA-Binding Proteins, Gene Deletion, Spliceosomes, Myogenic Regulatory Factors, Gene Targeting, COS Cells, Two-Hybrid System Techniques, Gene Expression Profiling, Protein Interaction Mapping, Immunoprecipitation, Mice, NAV1.6 Voltage-Gated Sodium Channel
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