title: New insights into the expression and function of neural connexins with transgenic mouse mutants.
abstract: Gap junctions represent direct intercellular conduits between contacting cells. The subunit proteins of these conduits are called connexins. To date, 20 and 21 connexin genes have been described in the mouse and human genome, respectively, many of them represent sequence-orthologous pairs. Targeted deletion of connexin genes in the mouse genome opened new insights into the biological function of these channel forming proteins, which, in some cases, could be correlated to phenotypic abnormalities in humans, suffering from inherited diseases caused by mutations in the corresponding orthologous connexin gene. Replacing the connexin coding DNA by an appropriate reporter gene has clarified in several cases its cell type specific expression in mouse brain. Various studies demonstrated that connexin36 is mainly expressed in interneurons of retina and brain. Targeted deletion of connexin36 evoked a loss of electrical signal transduction and interferes with synchrony which probably leads to defects in visual transmission and memory. Deletion of connexin43 in astrocytes of mouse brain resulted in increased spreading depression consistent with the notion of altered "spatial buffering" of K(+) ions and glutamate secreted by active neurons. General connexin30-deficiency led to hearing impairment and apoptosis of hair cells, similar to that observed in mice with cochlea specific deletion of connexin26. Reporter gene expression in connexin30-deficient mice indicated that astrocytes in certain brain regions and leptomeningeal as well as ependymal cells are labelled. Reporter gene expression in connexin45- and connexin47-deficient mice was used to reassign connexin45 expression to certain CNS neurons and connexin47 expression to oligodendrocytes.
authors.affiliation: Institut für Genetik, Abteilung Molekulargenetik, Universität Bonn, Römerstr. 164, 53117 Bonn, Germany.
authors.forename: Goran
authors.initials: G
authors.lastname: Söhl
authors.forename: Benjamin
authors.initials: B
authors.lastname: Odermatt
authors.forename: Stephan
authors.initials: S
authors.lastname: Maxeiner
authors.forename: Joachim
authors.initials: J
authors.lastname: Degen
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism* / Q000648:ultrastructure; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26