Ablation of connexin43 in smooth muscle cells of the mouse intestine: functional insights into physiology and morphology |
| |
Authors: | Britta Döring Gabriele Pfitzer Birgit Adam Tobias Liebregts Dominik Eckardt Gerald Holtmann Franz Hofmann Susanne Feil Robert Feil Klaus Willecke |
| |
Affiliation: | 1. Abteilung Molekulargenetik, Institut für Genetik, Universit?t Bonn, R?merstrasse 164, 53117, Bonn, Germany 3. Institut für Vegetative Physiologie, Universit?t K?ln, Cologne, Germany 4. Department of Gastroenterology, Hepatology and General Internal Medicine, Royal Adelaide Hospital, University of Adelaide, North Terrace, Adelaide, Australia 2. Max-Planck-Institut für Immunbiologie, Freiburg, Germany 5. Institut für Pharmakologie und Toxikologie, Technische Universit?t München, Munich, Germany 6. Interfakult?res Institut für Biochemie, Universit?t Tübingen, Tübingen, Germany
|
| |
Abstract: | Connexin43 (Cx43) gap-junction channels are highly abundant in intestinal smooth muscle but their functional impact has not been studied so far. Here, we have aimed to elucidate the functional role of Cx43 in the tunica muscularis of the mouse intestine in vivo. Transgenic mice with conditional deletion of Cx43 in smooth muscle cells (SMC) were generated. Histological investigations by immunofluorescence analyses and organ-bath recordings to assess the contractility of intestinal tissue strips were carried out. Measurements of gastrointestinal transit and of the visceromotor response by utilizing a standardized colorectal distension model to quantify alterations of visceral sensory function were also performed in SMC-specific Cx43 null mice and control littermates. Histologically, we found thickening of the tunica muscularis and a 13-fold increase of neutrophil infiltration of the gastrointestinal wall of SMC-specific Cx43 null mice. These animals also exhibited a decrease of 29% in gastrointestinal transit time. In contrast, the visceromotor response to a standardized colorectal distension was elevated, as was the contractility in SMC-specific Cx43 null mice, compared with controls. Thus, SMC-specific ablation of Cx43 in mice leads to morphological and functional alterations of the intestinal tunica muscularis, to gastrointestinal motor dysfunction and to altered visceral sensory function. This study was supported by a grant from the German Research Association (Wi 270/25-1,2) to K.W. and in part by the IFORES program of the University Hospital, Essen, Germany. |
| |
Keywords: | Gap junction Smooth muscle cell Cre/loxP Gut function Mouse (transgenic) |
本文献已被 PubMed SpringerLink 等数据库收录! |
|