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SCNM1, a Putative RNA Splicing Factor That Modifies Disease Severity in Mice
Abstract
The severity of many inherited disorders is influenced by genetic background. We describe a modifier interaction in C57BL/6Jmice that converts a chronic movement disorder into a lethal neurological disease. The primary mutation (med J ) changes a splice donor site of the sodium channel gene Scn8a (Na v 1.6). The modifier mutation is characteristic of strain C57BL/6Jand introduces a nonsense codon into sodium channel modifier 1 (SCNM1), a zinc finger protein and a putative splice factor. An internally deleted SCNM1 protein is also predicted as a result of exon skipping associated with disruption of a consensus exonic splicing enhancer. The effect of the modifier mutation is to reduce the abundance of correctly spliced sodium channel transcripts below the threshold for survival. Our finding that genetic variation in a putative RNA splicing factor influences disease susceptibility in mice raises the possibility that a similar mechanism modifies the severity of human inherited disorders.
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“a bacterial artificial chromosome transgene expressing wild-type Scnm1 can rescue the lethality and paralysis of Scn8amedJ in C57BL/6J mice154.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [154]
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Cites
Initial sequencing and analysis of the human genome
International Human Genome Sequencing Consortium, Whitehead Institute for Biomedical Research, C. F. G. R., Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon, K., Dewar, K., et al. (2001) · Nature · doi:10.1038/35057062 · Cited by 24,216
Efficient selection for high-expression transfectants with a novel eukaryotic vector
Niwa, H., Yamamura, K., & Miyazaki, J. (1991) · Gene · doi:10.1016/0378-1119(91)90434-d · Cited by 5,149
Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences
Mammalian Gene Collection (MGC) Program Team* (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.242603899 · Cited by 1,756
ESEfinder: a web resource to identify exonic splicing enhancers
Cartegni, L. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg616 · Cited by 1,593
Pre-mRNA splicing and human diseasePreprint
Faustino, N. A., & Cooper, T. A. (2003) · Genes & Development · doi:10.1101/gad.1048803 · Cited by 1,248
Genealogies of mouse inbred strains
Beck, J. A., Lloyd, S. E., Hafezparast, M., Lennon-Pierce, M., Eppig, J. T., Festing, M. F. W., & Fisher, E. (2000) · Nature Genetics · doi:10.1038/71641 · Cited by 825
Cartegni, L., & Krainer, A. R. (2002) · Nature Genetics · doi:10.1038/ng854 · Cited by 730
Sodium channel Na v 1.6 is localized at nodes of Ranvier, dendrites, and synapses
Caldwell, J. H., Schaller, K. L., Lasher, R. S., Peles, E., & Levinson, S. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090034797 · Cited by 649
Golling, G., Amsterdam, A., Sun, Z., Antonelli, M., Maldonado, E., Chen, W., Burgess, S. M., Haldi, M., Artzt, K., Farrington, S. M., et al. (2002) · Nature Genetics · doi:10.1038/ng896 · Cited by 544
Genomewide Analysis of mRNA Processing in Yeast Using Splicing-Specific Microarrays
Clark, T. A., Sugnet, C. W., & Ares, M. (2002) · Science · doi:10.1126/science.1069415 · Cited by 411
Mutation of a new sodium channel gene, Scn8a, in the mouse mutant ‘motor endplate disease’
Burgess, D. L., Kohrman, D. C., Galt, J., Plummer, N. W., Jones, J. M., Spear, B. T., & Meisler, M. H. (1995) · Nature Genetics · doi:10.1038/ng0895-461 · Cited by 307
Self-citationSplicing regulation as a potential genetic modifier
Nissim‐Rafinia, M., & Kerem, B. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(01)02619-1 · Cited by 224
Miki, R., Kadota, K., Bono, H. U., Mizuno, Y., Tomaru, Y., Carninci, P., Itoh, M., Shibata, K., Kawai, J., Konno, H., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.041605498 · Cited by 200
The U1 snRNP protein U1C recognizes the 5′ splice site in the absence of base pairing
Du, H., & Rosbash, M. (2002) · Nature · doi:10.1038/nature00947 · Cited by 169
Christophe, D., Christophe-Hobertus, C., & Pichon, B. (2000) · Cellular Signalling · doi:10.1016/s0898-6568(00)00077-2 · Cited by 165
Bedford, M. T., Reed, R., & Leder, P. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10602 · Cited by 161
Mutation Detection in the and Alleles of the Sodium Channel
Kohrman, D. C., Harris, J. B., & Meisler, M. H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.29.17576 · Cited by 140
Self-citationConfirmation of Quantitative Trait Loci for Alcohol Preference in Mice
Tarantino, L. M., McClearn, G. E., Rodriguez, L. A., & Plomin, R. J. (1998) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1998.tb03707.x · Cited by 125
Modifier genes and protective alleles in humans and mice.
Nadeau, J. (2003) · Current Opinion in Genetics and Development · doi:10.1016/s0959-437x(03)00061-3 · Cited by 118
Garrod, A. E. (1931) · Southern Medical Journal · doi:10.1097/00007611-193106000-00028 · Cited by 111
Kearney, J. A. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.22.2765 · Cited by 104
Defects in Pre-mRNA Processing as Causes of and Predisposition to Diseases
Stoilov, P., Meshorer, E., Gencheva, M., Glick, D., Soreq, H., & Stamm, S. (2002) · DNA and Cell Biology · doi:10.1089/104454902320908450 · Cited by 81
Sprunger, L. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.3.471 · Cited by 72
Sodium Channels and Neurological Disease: Insights from Scn8a Mutations in the Mouse
Meisler, M. H., Kearney, J., Escayg, A., Macdonald, B. T., & Sprunger, L. K. (2001) · The Neuroscientist · doi:10.1177/107385840100700208 · Cited by 68
Self-citationThe Inborn Factors in Disease: An Essay.
(1931) · JAMA · doi:10.1001/jama.1931.02730160056043 · Cited by 58
Nešić, D., & Krämer, A. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.19.6406-6417.2001 · Cited by 55
Genetic modifiers in human development and malformation syndromes, including chaperone proteins
Slavotinek, A. M. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg099 · Cited by 52
Cryns, K., Spaendonck, M. P. V., Flothmann, K., van Alphen, A. M., de Heyning, P. V., Timmermans, J., Zeeuw, C. I. D., & Camp, G. V. (2002) · Genome Research · doi:10.1101/gr.218402 · Cited by 12
Gravellese (2000) · Pure Amsterdam UMC · doi:10.1002/1529-0131(200002)43:2 · Cited by 2
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- D. A. Buchner M. Trudeau M. H. Meisler Genomics in press.
- We thank J. Heaton and T. Gelehrter for assistance with cell culture; L. Lawton and D. Burke for assistance with primer extension assays; S. Camper T. Glaser and J. Moran for critical review of the manuscript; and the Trans-NIH Mouse Sequencing Consortium and the University of Oklahoma Genome Center for the BAC sequence. Supported by NIH research grant GM24872 and training programs T32 GM07544 T32 HG00040 and T32 DC00011. Animal care was carried out in accordance with the Association for the Assessment and Accreditation of Laboratory Animal Care International.
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Wang, G., & Cooper, T. A. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2164 · Cited by 1,077
Herrmann, H. O., & Aebi, U. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073823 · Cited by 693
Genomic variants in exons and introns: identifying the splicing spoilers
Pagani, F., & Baralle, F. E. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1327 · Cited by 601
Alternative splicing in disease and therapy
Garcia-Blanco, M. A., Baraniak, A. P., & Lasda, E. L. (2004) · Nature Biotechnology · doi:10.1038/nbt964 · Cited by 527
Sodium channel mutations in epilepsy and other neurological disorders
Meisler, M. H. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25466 · Cited by 512
Self-citation
Metadata
- Authors
- Buchner, D. A., Trudeau, M., & Meisler, M. H.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Meisler, Miriam H.
- Venue
- Science
- Published
- 2003-08-15
- Volume
- 301
- Issue
- 5635
- Pages
- 967-969
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2160882954
- Cited by
- 137
- References
- 30
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 5 · 2016: 1 · 2015: 7 · 2014: 4 · 2013: 6 · 2012: 6
- FWCI
- 5.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Human Genome Research Institute (T32 HG-00040, T32HG000040)
- National Institute on Deafness and Other Communication Disorders (T32DC00011, T32DC000011)
- National Institute of General Medical Sciences (T32GM007544, R01GM024872, GM 24872, T32 GM07544)
- 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
- splicing factors, zinc finger proteins, SCN8A, Nav1.6, splice donor site mutation, nonsense mutation, genetic modifiers, disease severity, C57BL/6J mice, exonic splicing enhancers, exon skipping, movement disorders, genetic disorders
- MeSH terms
- RNA Splicing Factors, Alleles, Amino Acid Sequence, Animals, Carrier Proteins, Chromosome Mapping, Humans, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Neurologic Mutants, Mice, Transgenic, Molecular Sequence Data, Movement Disorders, Mutation, Nerve Tissue Proteins, Nervous System Diseases, Phenotype, Phylogeny, RNA Splicing, RNA, Messenger, Sodium Channels, Zinc Fingers, Codon, Terminator, Codon, Nonsense, Genetic Predisposition to Disease, Reverse Transcriptase Polymerase Chain Reaction, Mice, NAV1.6 Voltage-Gated Sodium Channel
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