Ablation of connexin43 in smooth muscle cells of the mouse intestine: functional insights into physiology and morphology.
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.
Döring
Britta
B
Abteilung Molekulargenetik, Institut für Genetik, Universität Bonn, Römerstrasse 164, 53117, Bonn, Germany.
Pfitzer
Gabriele
G
Adam
Birgit
B
Liebregts
Tobias
T
Eckardt
Dominik
D
Holtmann
Gerald
G
Hofmann
Franz
F
Feil
Susanne
S
Feil
Robert
R
Willecke
Klaus
K
D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D018031:Connexin 43 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000235:genetics; D019426:Integrases / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology / Q000503:physiopathology; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics; D009119:Muscle Contraction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D010147:Pain Measurement; D009195:Peroxidase / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D001616:beta-Galactosidase / Q000378:metabolism
D018031:Connexin 43; D008840:Microfilament Proteins; D009124:Muscle Proteins; C051615:transgelin; D013629:Tamoxifen; D011189:Potassium Chloride; D002217:Carbachol; D009195:Peroxidase; C045073:Cre recombinase; D019426:Integrases; D001616:beta-Galactosidase