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A dominant connexin43 mutant does not have dominant effects on gap junction coupling in astrocytes

Published online by Cambridge University Press:  04 March 2011

Sameh Wasseff ,
Charles K. Abrams  and
Steven S. Scherer
Sameh Wasseff*
Affiliation:
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Charles K. Abrams
Affiliation:
Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY, USA Department of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, NY, USA
Steven S. Scherer*
Affiliation:
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
*
Correspondence should be addressed to: Sameh Wasseff or Steven S. Scherer, Department of Neurology, University of Pennsylvania, 464 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104-6077, USA emails: swasseff@mail.med.upenn.edu; sscherer@mail.med.upenn.edu
Correspondence should be addressed to: Sameh Wasseff or Steven S. Scherer, Department of Neurology, University of Pennsylvania, 464 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104-6077, USA emails: swasseff@mail.med.upenn.edu; sscherer@mail.med.upenn.edu
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Abstract

Dominant mutations in GJA1, the gene encoding the gap junction protein connexin43 (Cx43), cause oculodentodigital dysplasia (ODDD), a syndrome affecting multiple tissues, including the central nervous system (CNS). We investigated the effects of the G60S mutant, which causes a similar, dominant phenotype in mice (Gja1Jrt/+). Astrocytes in acute brain slices from Gja1Jrt/+ mice transfer sulforhodamine-B comparably to that in their wild-type (WT) littermates. Further, astrocytes and cardiomyocytes cultured from Gja1Jrt/+ mice showed a comparable transfer of lucifer yellow to those from WT mice. In transfected cells, the G60S mutant formed gap junction (GJ) plaques but not functional channels. In co-transfected cells, the G60S mutant co-immunoprecipitated with WT Cx43, but did not diminish GJ coupling as measured by dual patch clamp. Thus, whereas G60S has dominant effects, it did not appreciably reduce GJ coupling.

Keywords

ODDDastrocytesconnexin
Type
Research Article
Information
Neuron Glia Biology , Volume 6 , Issue 4 , November 2010 , pp. 213 - 223
Copyright
Copyright © Cambridge University Press 2011

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