Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3

L K Sprunger; A Escayg; S Tallaksen-Greene; R L Albin; M H Meisler

doi:10.1093/hmg/8.3.471

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Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3

Journal article

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Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3

L K Sprunger, A Escayg, S Tallaksen-Greene, R L Albin and M H Meisler

Human molecular genetics, Vol.8(3), pp.471-479

03/1999

DOI: https://doi.org/10.1093/hmg/8.3.471

Handle:

https://hdl.handle.net/2376/114876

PMID: 9949206

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Abstract

Species Specificity

Dystonia - pathology

Humans

Mice, Inbred C57BL

Central Nervous System - pathology

Chromosome Mapping

Nerve Tissue Proteins - genetics

Mice, Inbred C3H

Dystonia - genetics

Homozygote

Phenotype

RNA Splicing

Animals

NAV1.6 Voltage-Gated Sodium Channel

Mice, Mutant Strains

Mice

Sodium Channels - genetics

Muscle, Skeletal - pathology

Mutation

Crosses, Genetic

Disease Models, Animal

The mouse mutant medJ contains a splice site mutation in the neuronal sodium channel Scn8a that results in a very low level of expression. On a C57BL/6J genetic background, medJ homozygotes exhibit progressive paralysis and juvenile lethality. The C3H genetic background has an ameliorating effect, producing viable adults with a novel dystonic phenotype. The dystonic mice exhibit movement-induced, sustained abnormal postures of the trunk and limbs. A dominant modifier locus responsible for the difference between strains was mapped to a 4.5 +/- 1.3 cM interval on mouse chromosome 3. Our findings establish a role for ion channels in dystonia and demonstrate the impact of genetic background on its severity and progression. This new model suggests that SCN8A on chromosome 12q13 and SCNM1 on chromosome 1p21-1q21 may contribute to human inherited dystonia.

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Title: Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3
Creators: L K Sprunger - Department of Human Genetics, University of Michigan and Geriatrics Research, Education and Clinical Center, VA Medical Center, Ann Arbor, MI 48109-0618, USA
A Escayg
S Tallaksen-Greene
R L Albin
M H Meisler
Publication Details: Human molecular genetics, Vol.8(3), pp.471-479
Academic Unit: Veterinary Medicine, College of
Publisher: England
Grant note: K08 HL02972 / NHLBI NIH HHS NS34509 / NINDS NIH HHS GM24872 / NIGMS NIH HHS
Identifiers: 99900547663301842
Language: English
Resource Type: Journal article