Glycine receptor β-subunit gene mutation in spastic mouse associated with LINE-1 element insertion

Stephen F. Kingsmore, Bruno Giros, David Suh, Mark Bieniarz, Marc G. Caron, Michael F Seldin

Research output: Contribution to journalArticle

177 Citations (Scopus)

Abstract

Congenital myoclonus is a widespread neurologic disorder characterized by hyperexcitability, muscular spasticity and myoclonus associated with marked reduction in neural glycine binding sites. The recessive mouse mutation spastic (spa) is a prototype of inherited myoclonus. Here we show that defects in the gene encoding the β-subunit of the glycine receptor (Glrb) underlie spa: Glrb maps to the same region of mouse chromosome 3 as spa, and Glrb mRNA is markedly reduced throughout brains of spa mice, most likely as a result of an insertional mutation of a 7.1 kilobase LINE-1 element within intron 6 of Glrb. These results provide evidence that Glrb is necessary for postsynaptic expression of glycine receptor complexes, and suggest Glrb as a candidate gene for inherited myoclonus in other species.

Original languageEnglish (US)
Pages (from-to)136-142
Number of pages7
JournalNature Genetics
Volume7
Issue number2
DOIs
StatePublished - Jun 1994
Externally publishedYes

Fingerprint

Long Interspersed Nucleotide Elements
Glycine Receptors
Myoclonus
Muscle Spasticity
Mutation
Genes
Chromosomes, Human, Pair 3
Nervous System Diseases
Glycine
Introns
Binding Sites
Messenger RNA
Brain

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Glycine receptor β-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. / Kingsmore, Stephen F.; Giros, Bruno; Suh, David; Bieniarz, Mark; Caron, Marc G.; Seldin, Michael F.

In: Nature Genetics, Vol. 7, No. 2, 06.1994, p. 136-142.

Research output: Contribution to journalArticle

Kingsmore, Stephen F. ; Giros, Bruno ; Suh, David ; Bieniarz, Mark ; Caron, Marc G. ; Seldin, Michael F. / Glycine receptor β-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. In: Nature Genetics. 1994 ; Vol. 7, No. 2. pp. 136-142.
@article{16d351fc11ac4314bd478b855b51cc21,
title = "Glycine receptor β-subunit gene mutation in spastic mouse associated with LINE-1 element insertion",
abstract = "Congenital myoclonus is a widespread neurologic disorder characterized by hyperexcitability, muscular spasticity and myoclonus associated with marked reduction in neural glycine binding sites. The recessive mouse mutation spastic (spa) is a prototype of inherited myoclonus. Here we show that defects in the gene encoding the β-subunit of the glycine receptor (Glrb) underlie spa: Glrb maps to the same region of mouse chromosome 3 as spa, and Glrb mRNA is markedly reduced throughout brains of spa mice, most likely as a result of an insertional mutation of a 7.1 kilobase LINE-1 element within intron 6 of Glrb. These results provide evidence that Glrb is necessary for postsynaptic expression of glycine receptor complexes, and suggest Glrb as a candidate gene for inherited myoclonus in other species.",
author = "Kingsmore, {Stephen F.} and Bruno Giros and David Suh and Mark Bieniarz and Caron, {Marc G.} and Seldin, {Michael F}",
year = "1994",
month = "6",
doi = "10.1038/ng0694-136",
language = "English (US)",
volume = "7",
pages = "136--142",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Glycine receptor β-subunit gene mutation in spastic mouse associated with LINE-1 element insertion

AU - Kingsmore, Stephen F.

AU - Giros, Bruno

AU - Suh, David

AU - Bieniarz, Mark

AU - Caron, Marc G.

AU - Seldin, Michael F

PY - 1994/6

Y1 - 1994/6

N2 - Congenital myoclonus is a widespread neurologic disorder characterized by hyperexcitability, muscular spasticity and myoclonus associated with marked reduction in neural glycine binding sites. The recessive mouse mutation spastic (spa) is a prototype of inherited myoclonus. Here we show that defects in the gene encoding the β-subunit of the glycine receptor (Glrb) underlie spa: Glrb maps to the same region of mouse chromosome 3 as spa, and Glrb mRNA is markedly reduced throughout brains of spa mice, most likely as a result of an insertional mutation of a 7.1 kilobase LINE-1 element within intron 6 of Glrb. These results provide evidence that Glrb is necessary for postsynaptic expression of glycine receptor complexes, and suggest Glrb as a candidate gene for inherited myoclonus in other species.

AB - Congenital myoclonus is a widespread neurologic disorder characterized by hyperexcitability, muscular spasticity and myoclonus associated with marked reduction in neural glycine binding sites. The recessive mouse mutation spastic (spa) is a prototype of inherited myoclonus. Here we show that defects in the gene encoding the β-subunit of the glycine receptor (Glrb) underlie spa: Glrb maps to the same region of mouse chromosome 3 as spa, and Glrb mRNA is markedly reduced throughout brains of spa mice, most likely as a result of an insertional mutation of a 7.1 kilobase LINE-1 element within intron 6 of Glrb. These results provide evidence that Glrb is necessary for postsynaptic expression of glycine receptor complexes, and suggest Glrb as a candidate gene for inherited myoclonus in other species.

UR - http://www.scopus.com/inward/record.url?scp=0028175530&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028175530&partnerID=8YFLogxK

U2 - 10.1038/ng0694-136

DO - 10.1038/ng0694-136

M3 - Article

C2 - 7920630

AN - SCOPUS:0028175530

VL - 7

SP - 136

EP - 142

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -