Ablation of connexin43 in uterine smooth muscle cells of the mouse causes delayed parturition.
Gap junctions are characteristically increased in the myometrium during term and preterm delivery and are thought to be essential for the development of uterine contractions during labour. Expression of connexin43 (Cx43), the major myometrial gap junction protein, is increased during delivery. We have generated a mouse mutant (Cx43fl/fl:SM-CreERT2), in which the coding region of Cx43 can be specifically deleted in smooth muscle cells at any given time point by application of tamoxifen. By this approach, we were able to study long-term effects on myometrial functions that are necessary for parturition as well as gap junction intercellular communication in primary myometrial cell cultures. We found a prolongation of the pregnancy in 82% of tamoxifen-treated Cx43fl/fl:SM-CreERT2 mice as well as decreased dye coupling in cultured primary myocytes of these animals. Other parturition-specific parameters such as the regulation of oxytocin receptor, prostaglandin F receptor or progesterone remained unchanged. Our results indicate the important function of Cx43 during parturition in the living animal and suggest further strategies to investigate the role of connexins in uterine contractility in transgenic mice.
Döring
Britta
B
Institut für Genetik, Abteilung Molekulargenetik, Universität Bonn, Römerstr. 164, 53117 Bonn, Germany.
Shynlova
Oksana
O
Tsui
Prudence
P
Eckardt
Dominik
D
Janssen-Bienhold
Ulrike
U
Hofmann
Franz
F
Feil
Susanne
S
Feil
Robert
R
Lye
Stephen J
SJ
Willecke
Klaus
K
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000378:metabolism; D005260:Female; D017629:Gap Junctions / Q000737:chemistry / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D016762:Genes, fos; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D009215:Myometrium / Q000166:cytology*; D036801:Parturition / Q000502:physiology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011374:Progesterone / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000378:metabolism
D018031:Connexin 43; D004965:Estrogen Antagonists; D013629:Tamoxifen; D011374:Progesterone