Biological Functions of Connexin Genes Revealed by Human Genetic Defects, Dominant Negative Approaches and Targeted Deletions in the Mouse

Novartis Found Symp. 1999;219:76-88; discussion 88-96. doi: 10.1002/9780470515587.ch6.


Gap junction channels in mammalian organs can be built up of at least 13 different connexin proteins, most of which are expressed in only few cell types, although many cells express more than one connexin protein. Recently, the consequences of missing or defective connexin proteins were studied in human patients with defects in connexin32 (Cx32; beta 1; X-linked Charcot-Marie-Tooth disease) or in Cx26 (beta 2; non-syndromic sensorineural deafness), and in mice with targeted deletions in the Cx26, Cx32, Cx37 (alpha 4), Cx43 (alpha 1), Cx46 (alpha 3) or Cx50 (alpha 8) genes. Some effects of dominant negative mutations in connexin genes have been characterized in Xenopus oocytes and transfected mammalian cells in culture. Here we review results of these different experimental approaches and report new findings regarding the characterization of Cx40 (alpha 5)- and Cx31 (beta 3)-deficient mice. The phenotypic alterations, caused by different defective connexin genes in mice or humans, are divergent, although in most known cases the viability is not affected. When more than one connexin gene, coexpressed in the same cell, is inactivated, development or maturation can be more severely affected at an earlier stage. Some connexin proteins, if present in the same cell, can partially replace each other in certain functions. Thus, the diversity of connexin proteins in mammalian cells may provide functional overlap and complementation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Connexin 43 / genetics
  • Connexins / genetics*
  • Gene Targeting
  • Genetic Diseases, Inborn / genetics
  • Humans
  • Mice
  • Mutagenesis


  • Connexin 43
  • Connexins
  • DFNA3 protein, human
  • connexin 32