Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current

Jim Berg, Hong Jiang, Charles A. Thornton, Stephen C. Cannon

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: Muscle fiber degeneration and myotonic discharges are the hallmarks of myotonic dystrophy (DM). The molecular basis for the myotonia was recently tied to abnormal splicing of the chloride channel (ClC-1) pre-mRNA, often resulting in UAG premature termination, which leads to decreased channel protein and therefore a reduced resting chloride conductance. Methods: The authors assessed the functional properties of two commonly occurring DM mRNA splice variants by expression in oocytes. Results: Neither splice variant coded for a functional Cl- channel. Co-injection of alternative splice variants with wild-type ClC-1 cRNA reduced the current density and accelerated channel closure upon repolarization of the membrane. Conclusions: These data show that the aberrantly spliced chloride channel message exerts a dominant negative effect that may contribute to the development of myotonia.

Original languageEnglish (US)
Pages (from-to)2371-2375
Number of pages5
JournalNeurology
Volume63
Issue number12
StatePublished - Dec 28 2004

Fingerprint

Myotonia
Myotonic Dystrophy
Chloride Channels
Complementary RNA
Messenger RNA
RNA Precursors
Oocytes
Chlorides
Muscles
Injections
Membranes
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Berg, J., Jiang, H., Thornton, C. A., & Cannon, S. C. (2004). Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current. Neurology, 63(12), 2371-2375.

Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current. / Berg, Jim; Jiang, Hong; Thornton, Charles A.; Cannon, Stephen C.

In: Neurology, Vol. 63, No. 12, 28.12.2004, p. 2371-2375.

Research output: Contribution to journalArticle

Berg, J, Jiang, H, Thornton, CA & Cannon, SC 2004, 'Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current', Neurology, vol. 63, no. 12, pp. 2371-2375.
Berg J, Jiang H, Thornton CA, Cannon SC. Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current. Neurology. 2004 Dec 28;63(12):2371-2375.
Berg, Jim ; Jiang, Hong ; Thornton, Charles A. ; Cannon, Stephen C. / Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current. In: Neurology. 2004 ; Vol. 63, No. 12. pp. 2371-2375.
@article{beaefef0431b45abb98d6df0d0c0f4e2,
title = "Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current",
abstract = "Background: Muscle fiber degeneration and myotonic discharges are the hallmarks of myotonic dystrophy (DM). The molecular basis for the myotonia was recently tied to abnormal splicing of the chloride channel (ClC-1) pre-mRNA, often resulting in UAG premature termination, which leads to decreased channel protein and therefore a reduced resting chloride conductance. Methods: The authors assessed the functional properties of two commonly occurring DM mRNA splice variants by expression in oocytes. Results: Neither splice variant coded for a functional Cl- channel. Co-injection of alternative splice variants with wild-type ClC-1 cRNA reduced the current density and accelerated channel closure upon repolarization of the membrane. Conclusions: These data show that the aberrantly spliced chloride channel message exerts a dominant negative effect that may contribute to the development of myotonia.",
author = "Jim Berg and Hong Jiang and Thornton, {Charles A.} and Cannon, {Stephen C.}",
year = "2004",
month = "12",
day = "28",
language = "English (US)",
volume = "63",
pages = "2371--2375",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

TY - JOUR

T1 - Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current

AU - Berg, Jim

AU - Jiang, Hong

AU - Thornton, Charles A.

AU - Cannon, Stephen C.

PY - 2004/12/28

Y1 - 2004/12/28

N2 - Background: Muscle fiber degeneration and myotonic discharges are the hallmarks of myotonic dystrophy (DM). The molecular basis for the myotonia was recently tied to abnormal splicing of the chloride channel (ClC-1) pre-mRNA, often resulting in UAG premature termination, which leads to decreased channel protein and therefore a reduced resting chloride conductance. Methods: The authors assessed the functional properties of two commonly occurring DM mRNA splice variants by expression in oocytes. Results: Neither splice variant coded for a functional Cl- channel. Co-injection of alternative splice variants with wild-type ClC-1 cRNA reduced the current density and accelerated channel closure upon repolarization of the membrane. Conclusions: These data show that the aberrantly spliced chloride channel message exerts a dominant negative effect that may contribute to the development of myotonia.

AB - Background: Muscle fiber degeneration and myotonic discharges are the hallmarks of myotonic dystrophy (DM). The molecular basis for the myotonia was recently tied to abnormal splicing of the chloride channel (ClC-1) pre-mRNA, often resulting in UAG premature termination, which leads to decreased channel protein and therefore a reduced resting chloride conductance. Methods: The authors assessed the functional properties of two commonly occurring DM mRNA splice variants by expression in oocytes. Results: Neither splice variant coded for a functional Cl- channel. Co-injection of alternative splice variants with wild-type ClC-1 cRNA reduced the current density and accelerated channel closure upon repolarization of the membrane. Conclusions: These data show that the aberrantly spliced chloride channel message exerts a dominant negative effect that may contribute to the development of myotonia.

UR - http://www.scopus.com/inward/record.url?scp=11144260152&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11144260152&partnerID=8YFLogxK

M3 - Article

C2 - 15623702

AN - SCOPUS:11144260152

VL - 63

SP - 2371

EP - 2375

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 12

ER -