HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 6, 2997-3001, February 8, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/6/2997    most recent R700041200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laird, D. W. Search for Related Content PubMed PubMed Citation Articles by Laird, D. W. Social Bookmarking                      What's this?

Minireview

Closing the Gap on Autosomal Dominant Connexin-26 and Connexin-43 Mutants Linked to Human Disease^*

From the Departments of Anatomy & Cell Biology and Physiology & Pharmacology, University of Western Ontario, London, Ontario N6A 5C1, Canada

Cells within the vast majority of human tissues communicate directly through clustered arrays of intercellular channels called gap junctions. Gene ablation studies in mouse models have revealed that these intercellular channels are necessary for a variety of organ functions and that some of these genes are essential for survival. Molecular genetics has uncovered that germ line mutations in nearly half of the genes that encode the 21-member connexin family of gap junction proteins are linked to one or more human diseases. Frequently, these mutations are autosomal recessive, whereas in other cases, autosomal dominant mutations manifest as disease. Given the broad and overlapping distribution of connexins in a wide arrangement of tissues, it is hard to predict where connexin-linked diseases will clinically manifest. For instance, the most prevalent connexin in the human body is connexin-43 (Cx43), yet autosomal dominant mutations in the GJA1 gene, which encodes Cx43, exhibit modest developmental disorders resulting in a disease termed oculodentodigital dysplasia. Autosomal recessive mutations in the gene encoding Cx26 result in moderate to severe sensorineural hearing loss, whereas autosomal dominant mutations produce hearing loss and a wide range of skin diseases, including palmoplantar keratoderma. Here, we will focus on autosomal dominant mutations of the genes encoding Cx26 and Cx43 in relation to models that link genotypes to phenotypic outcomes with particular reference to how these approaches provide insight into human disease.

^* This minireview will be reprinted in the 2008 Minireview Compendium, which will be available in January, 2009. This work was supported by the Canadian Institutes of Health Research and the Canada Research Chair Program.

¹ To whom correspondence should be addressed. Tel.: 519-661-2111 (ext. 86827); E-mail: dale.laird{at}schulich.uwo.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Das, T. D. Smith, J. D. Sarma, J. D. Ritzenthaler, J. Maza, B. E. Kaplan, L. A. Cunningham, L. Suaud, M. J. Hubbard, R. C. Rubenstein, et al. ERp29 Restricts Connexin43 Oligomerization in the Endoplasmic Reticulum Mol. Biol. Cell, May 15, 2009; 20(10): 2593 - 2604. [Abstract] [Full Text] [PDF]

				J. Simek, J. Churko, Q. Shao, and D. W. Laird Cx43 has distinct mobility within plasma-membrane domains, indicative of progressive formation of gap-junction plaques J. Cell Sci., February 15, 2009; 122(4): 554 - 562. [Abstract] [Full Text] [PDF]