title: A new conditional mouse mutant reveals specific expression and functions of connexin36 in neurons and pancreatic beta-cells.
abstract: Connexin36 (Cx36) is the main connexin isoform expressed in neurons of the central nervous system (CNS) and in pancreatic beta-cells, i.e. two types of excitable cells that share - in spite of their different origins - a number of common features. Previous studies on Cx36 deficient mice have documented that loss of Cx36 resulted in phenotypic abnormalities in both the CNS and the pancreas which, however, could not be attributed to specific cell types due to the general deletion nature of the animal model used. Attempts to address this limitation using cell type specific deletions generated by the Cre/loxP strategy have so far been complicated by the lack of Cx36 expression from the floxed allele. We have now generated a conditional Cx36 deficient mouse mutant in which the coding region of Cx36 is flanked by loxP sites, followed by a cyan fluorescent protein (CFP) reporter gene. Here we show that Cx36 was still expressed from the floxed allele in neurons and pancreatic beta-cells. In these cells, a 30-60% decrease of this protein, relative to the expression level of the wildtype allele, did not significantly perturb cell coupling. The deletion of Cx36 by ubiquitously and cell type specifically expressed Cre recombinases revealed that CFP functions as a reliable reporter for Cx36 expression in brain neurons and to some extent in retina neurons, but not in pancreas. Loss of Cx36 by Cre-mediated recombination was documented at transcript and protein levels. Cell type specific deletion of Cx36 in the endocrine pancreas revealed major alterations in the basal as well as the glucose-induced insulin secretion, hence specifically attributing to pancreatic Cx36 an important regulatory role in the control of beta-cell function. Cell type specific deletion of Cx36 in the CNS by suitable Cre recombinases should also help to elucidate the functional role of Cx36 in different neuronal subtypes.
authors.affiliation: Institute of Genetics, Division of Molecular Genetics, University of Bonn, Roemerstrasse 164, Bonn, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wellershaus
authors.forename: Joachim
authors.initials: J
authors.lastname: Degen
authors.forename: Jim
authors.initials: J
authors.lastname: Deuchars
authors.forename: Martin
authors.initials: M
authors.lastname: Theis
authors.forename: Anne
authors.initials: A
authors.lastname: Charollais
authors.forename: Dorothée
authors.initials: D
authors.lastname: Caille
authors.forename: Benoit
authors.initials: B
authors.lastname: Gauthier
authors.forename: Ulrike
authors.initials: U
authors.lastname: Janssen-Bienhold
authors.forename: Stephan
authors.initials: S
authors.lastname: Sonntag
authors.forename: Pedro
authors.initials: P
authors.lastname: Herrera
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology; D017630:Connexins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000737:chemistry* / Q000378:metabolism; D019426:Integrases; D051379:Mice; D009474:Neurons / Q000737:chemistry*; D012160:Retina / Q000166:cytology; D014018:Tissue Distribution; D000097004:Gap Junction delta-2 Protein
chemical_list: D017630:Connexins; D007328:Insulin; D019426:Integrases; D000097004:Gap Junction delta-2 Protein; C045073:Cre recombinase