The neuronal voltage-gated sodium channel, Scn8a, is essential for postnatal maturation of spinal, but not oculomotor, motor units

John D. Porter; Linda A. Goldstein; Edward J. Kasarskis; Jennifer K. Brueckner; Brett T. Spear

doi:10.1006/exnr.1996.0107

The neuronal voltage-gated sodium channel, Scn8a, is essential for postnatal maturation of spinal, but not oculomotor, motor units

John D. Porter, Linda A. Goldstein, Edward J. Kasarskis, Jennifer K. Brueckner, Brett T. Spear

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Mice with a nontargeted transgene insertion at the motor endplate disease (med) locus (med(tg)) contain a deletion of a novel gene encoding a neuronal voltage-gated sodium channel, designated Scn8a (4). We characterized severe skeletal muscle atrophy beginning by Postnatal Day 10 (P10) and death by P20 in the med(tg) mouse. Denervation was functional, rather than structural, since the Scn8a mutation was not accompanied by retraction of neuromuscular contacts, motoneuron death, or decreased motoneuron soma diameter. Although pathology consistent with denervation was seen in both hindlimb and forelimb musculature, the postnatal maturation of the extraocular muscles was not altered. The onset of paralysis is likely coincident with the time that the Scn8a sodium channel normally assumes a critical role in the initiation and/or propagation of action potentials in spinal motoneurons. By contrast, the lack of consequences for extraocular muscle suggests that the Scn8a voltage-gated sodium channel may be of relatively minor importance for oculomotor motoneurons.

Original language	English
Pages (from-to)	328-334
Number of pages	7
Journal	Experimental Neurology
Volume	139
Issue number	2
DOIs	https://doi.org/10.1006/exnr.1996.0107
State	Published - Jun 1996

Bibliographical note

Funding Information:
We thank Michael Green (University of Kentucky Transgenic Mouse Facility) for production of the transgenic mice and Amy Ellis, Mary Gail Engle, and Olga Itkis for technical assistance. Drs. Brian Davis and Dale Sengelaub provided assistance with these studies. We also thank Dr. Jonathan Satin for many helpful discussions and for comments on an earlier version of the manuscript. The A4.74 and A4.840 monoclonal antibodies developed by Dr. H. Blau were provided by the Developmental Studies Hybridoma Bank. This work was supported by National Eye Institute Grant EY09834 and a Lew R. Wasserman Merit Award from Research to Prevent Blindness to J.D.P., Council for Tobacco Research Grant 3512 to B.T.S, a VA Research Service Grant and T32 ES07265 to E.J.K, and an unrestricted grant from Research to Prevent Blindness.

ASJC Scopus subject areas

Neurology
Developmental Neuroscience

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title = "The neuronal voltage-gated sodium channel, Scn8a, is essential for postnatal maturation of spinal, but not oculomotor, motor units",

abstract = "Mice with a nontargeted transgene insertion at the motor endplate disease (med) locus (med(tg)) contain a deletion of a novel gene encoding a neuronal voltage-gated sodium channel, designated Scn8a (4). We characterized severe skeletal muscle atrophy beginning by Postnatal Day 10 (P10) and death by P20 in the med(tg) mouse. Denervation was functional, rather than structural, since the Scn8a mutation was not accompanied by retraction of neuromuscular contacts, motoneuron death, or decreased motoneuron soma diameter. Although pathology consistent with denervation was seen in both hindlimb and forelimb musculature, the postnatal maturation of the extraocular muscles was not altered. The onset of paralysis is likely coincident with the time that the Scn8a sodium channel normally assumes a critical role in the initiation and/or propagation of action potentials in spinal motoneurons. By contrast, the lack of consequences for extraocular muscle suggests that the Scn8a voltage-gated sodium channel may be of relatively minor importance for oculomotor motoneurons.",

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AU - Goldstein, Linda A.

AU - Kasarskis, Edward J.

AU - Brueckner, Jennifer K.

AU - Spear, Brett T.

PY - 1996/6

Y1 - 1996/6

N2 - Mice with a nontargeted transgene insertion at the motor endplate disease (med) locus (med(tg)) contain a deletion of a novel gene encoding a neuronal voltage-gated sodium channel, designated Scn8a (4). We characterized severe skeletal muscle atrophy beginning by Postnatal Day 10 (P10) and death by P20 in the med(tg) mouse. Denervation was functional, rather than structural, since the Scn8a mutation was not accompanied by retraction of neuromuscular contacts, motoneuron death, or decreased motoneuron soma diameter. Although pathology consistent with denervation was seen in both hindlimb and forelimb musculature, the postnatal maturation of the extraocular muscles was not altered. The onset of paralysis is likely coincident with the time that the Scn8a sodium channel normally assumes a critical role in the initiation and/or propagation of action potentials in spinal motoneurons. By contrast, the lack of consequences for extraocular muscle suggests that the Scn8a voltage-gated sodium channel may be of relatively minor importance for oculomotor motoneurons.

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The neuronal voltage-gated sodium channel, Scn8a, is essential for postnatal maturation of spinal, but not oculomotor, motor units

Abstract

Bibliographical note

ASJC Scopus subject areas

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