CoChat
Sign Up
Cited by 140RNA Research and SplicingIon channel regulation and functionCardiac electrophysiology and arrhythmias

Mutation Detection in the and Alleles of the Sodium Channel

Open access
Kohrman, David C., Harris, John B., Meisler, Miriam H.·1996·Journal of Biological Chemistry
DOI 10.1074/jbc.271.29.17576
Open this paper in CoChat — free account

Abstract

Analysis of a transgene-induced mutation at the mouse med locus led to the identification of the novel voltage-gated sodium channel gene Scn8a (Burgess, D. L., Kohrman, D. C., Galt, J., Plummer, N. W., Jones, J. M., Spear, B., and Meisler, M. H.(1995) Nat. Genet. 10, 461-465). We now report the identification of splicing defects in two spontaneous mutations of Scn8a. The original med mutation was caused by insertion of a truncated LINE element into exon 2 of Scn8a. The med transcript is spliced from exon 1 to a cryptic acceptor site in intron 2. A 4-base pair deletion within the 5' donor site of exon 3 in the medJ allele results in splicing from exon 1 to exon 4. Both mutant transcripts have altered reading frames with premature stop codons close to the N terminus of the protein. Loss of Scn8a expression results in progressive paralysis and early death. Intron 2 of Scn8a is flanked by minor class AT-AC splice sites. The observed splicing patterns of the med and medJ mutant transcripts provide the first evidence for preferential in vivo splicing between donor and acceptor sites of the same class. The apparent functional incompatibility may be a consequence of the different composition of spliceosomes bound to major and minor splice sites.

Integrity signals

Registry

Crossref · 10.1074/jbc.271.29.17576

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The medJ mutation has a four base pair deletion in the 5′ splice site of intron 3 and causes skipping of both exons 2 and 3 in a majority of Scn8a transcripts.

    “This mutation, medJ, does not alter the coding sequence of Scn8a but instead has a four base pair deletion in the 5′ splice site of intron 3, which causes skipping of both exons 2 and 3 in a majority of Scn8a transcripts”

    From The neurogenetics of alternative splicing (2016) · cites this paper as [148]

  • An Scn8a splicing mutation causes severe neurological defects.

    “Forward genetic studies have identified an Scn8a splicing mutation that causes severe neurological defects.”

    From The neurogenetics of alternative splicing (2016) · cites this paper as [148]

  • The medJ mutation produces a severely truncated, non-functional Nav1.6 protein.

    “and produces a severely truncated, non-functional Nav1.6 protein148.”

    From The neurogenetics of alternative splicing (2016) · cites this paper as [148]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Kohrman, D. C., Harris, J. B., & Meisler, M. H.
Affiliations
  • University of Michigan (US)
  • Newcastle upon Tyne Hospital (GB)
Corresponding author
Meisler, Miriam H.
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1996-07
Volume
271
Issue
29
Pages
17576-17581
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.271.29.17576
OpenAlex
W2069192199
Cited by
140
References
44
Citations by year
2025: 1 · 2024: 2 · 2023: 3 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 4
FWCI
4.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (R01GM024872, GM 24872)
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
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords
SCN8A, voltage-gated sodium channels, aberrant splicing, cryptic splice site, spliceosome, premature stop codon, progressive paralysis, mouse mutations
MeSH terms
Alleles, Amino Acid Sequence, Animals, Base Sequence, Brain, Exons, Genes, Recessive, Humans, Introns, Mice, Inbred AKR, Mice, Inbred C57BL, Mice, Neurologic Mutants, Mice, Transgenic, Molecular Sequence Data, Nerve Tissue Proteins, Sequence Homology, Nucleic Acid, Transcription, Genetic, Sodium Channels, Motor Neuron Disease, Point Mutation, Alternative Splicing, DNA Primers, Mice, NAV1.6 Voltage-Gated Sodium Channel

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review