{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:38:06Z","timestamp":1791034686018,"version":"4.1.0"},"reference-count":44,"publisher":"The Company of Biologists","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,5,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1242\/jcs.02892","type":"journal-article","created":{"date-parts":[[2006,4,4]],"date-time":"2006-04-04T20:14:50Z","timestamp":1144181690000},"page":"1715-1722","source":"Crossref","is-referenced-by-count":102,"title":["Ablation of connexin43 in uterine smooth muscle cells of the mouse causes delayed parturition"],"prefix":"10.1242","volume":"119","author":[{"given":"Britta","family":"Do\u0308ring","sequence":"first","affiliation":[{"name":"Institut fu\u0308r Genetik, Abteilung Molekulargenetik, Universita\u0308t Bonn, Ro\u0308merstr. 164, 53117 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana","family":"Shynlova","sequence":"additional","affiliation":[{"name":"Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prudence","family":"Tsui","sequence":"additional","affiliation":[{"name":"Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Eckardt","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Genetik, Abteilung Molekulargenetik, Universita\u0308t Bonn, Ro\u0308merstr. 164, 53117 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Janssen-Bienhold","sequence":"additional","affiliation":[{"name":"Neurobiologie, Carl von Ossietzky Universita\u0308t Oldenburg, Oldenburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Pharmakologie und Toxikologie, Technische Universita\u0308t Mu\u0308nchen, Mu\u0308nchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Feil","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Pharmakologie und Toxikologie, Technische Universita\u0308t Mu\u0308nchen, Mu\u0308nchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Feil","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Pharmakologie und Toxikologie, Technische Universita\u0308t Mu\u0308nchen, Mu\u0308nchen, Germany"},{"name":"Interfakulta\u0308res Institut fu\u0308r Biochemie, Universita\u0308t Tu\u0308bingen, Tu\u0308bingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Lye","sequence":"additional","affiliation":[{"name":"Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada"},{"name":"Institute of Medical Science, University of Toronto, Toronto, ON, Canada"},{"name":"Departments of Obstetrics and Gynecology and Physiology, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Willecke","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Genetik, Abteilung Molekulargenetik, Universita\u0308t Bonn, Ro\u0308merstr. 164, 53117 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042519551549600_REF1","doi-asserted-by":"crossref","unstructured":"Albrecht, J. L., Atal, N. S., Tadros, P. N., Orsino, A., Lye. S. J., Sadovsky. Y. and Beyer. E. C. (1996). Rat uterine myometrium contains the gap junction protein connexin45, which has a differing temporal expression pattern from connexin43. Am. J. Obstet. Gynecol.175, 853-858.","DOI":"10.1016\/S0002-9378(96)80012-3"},{"key":"2021042519551549600_REF2","doi-asserted-by":"crossref","unstructured":"Al-Matubsi, H. Y., Eis, A. L., Brodt-Eppley, J., MacPhee, D. J., Lye. S. and Myatt. L. (2001). Expression and localization of the contractile prostaglandin F receptor in pregnant rat myometrium in late gestation, labor, and postpartum. Biol. Reprod.65, 1029-1037.","DOI":"10.1095\/biolreprod65.4.1029"},{"key":"2021042519551549600_REF3","doi-asserted-by":"crossref","unstructured":"Arosh, J. A., Banu, S. K., Chapdelaine, P. and Fortier, M. A. (2004). Temporal and tissue-specific expression of prostaglandin receptors EP2, EP3, EP4, FP, and cyclooxygenases 1 and 2 in uterus and fetal membranes during bovine pregnancy. Endocrinology145, 407-417.","DOI":"10.1210\/en.2003-1007"},{"key":"2021042519551549600_REF4","doi-asserted-by":"crossref","unstructured":"Balducci, J., Risek, B., Gilula, N. B., Hand, A., Egan, J. F. and Vintzileos, A. M. (1993). Gap junction formation in human myometrium: a key to preterm labor? Am. J. Obstet. Gynecol.168, 1609-1615.","DOI":"10.1016\/S0002-9378(11)90806-0"},{"key":"2021042519551549600_REF5","doi-asserted-by":"crossref","unstructured":"Barros, F. C., Victora, C. G., Barros, A. J., Santos, I. S., Albernaz, E., Matijasevich, A., Domingues, M. R., Sclowitz, I. K., Hallal, P. C., Silveira, M. F. et al. (2005). The challenge of reducing neonatal mortality in middle-income countries: findings from three Brazilian birth cohorts in 1982, 1993, and 2004. Lancet365, 847-854.","DOI":"10.1016\/S0140-6736(05)71042-4"},{"key":"2021042519551549600_REF6","unstructured":"Bibby, E. and Stewart, A. (2004). The epidemiology of preterm birth. Neuro Endocrinol. Lett.25, 43-47."},{"key":"2021042519551549600_REF7","unstructured":"Challis, J. R. G. and Lye, S. J. (1994). The physiology of reproduction. In Parturition (ed. F. Knobil and J. D. Neill), pp. 985-1031. New York: Raven Press."},{"key":"2021042519551549600_REF8","doi-asserted-by":"crossref","unstructured":"Chow, L. and Lye, S. J. (1994). Expression of the gap junction protein connexin-43 is increased in the human myometrium toward term and with the onset of labor. Am. J. Obstet. Gynecol.170, 788-795.","DOI":"10.1016\/S0002-9378(94)70284-5"},{"key":"2021042519551549600_REF9","doi-asserted-by":"crossref","unstructured":"Cook, J. L., Zaragoza, D. B., Sung, D. H. and Olson, D. M. (2000). Expression of myometrial activation and stimulation genes in a mouse model of preterm labor: myometrial activation, stimulation, and preterm labor. Endocrinology141, 1718-1728.","DOI":"10.1210\/endo.141.5.7474"},{"key":"2021042519551549600_REF10","doi-asserted-by":"crossref","unstructured":"Eckardt, D., Theis, M., Do\u0308ring, B., Speidel, D., Willecke, K. and Ott, T. (2004). Spontaneous ectopic recombination in cell-type-specific Cre mice removes loxP-flanked marker cassettes in vivo. Genesis38, 159-165.","DOI":"10.1002\/gene.20011"},{"key":"2021042519551549600_REF11","doi-asserted-by":"crossref","unstructured":"Feil, R., Brocard, J., Mascrez, B., LeMeur, M., Metzger, D. and Chambon, P. (1996). Ligand-activated site-specific recombination in mice. Proc. Natl. Acad. Sci. USA93, 10887-10890.","DOI":"10.1073\/pnas.93.20.10887"},{"key":"2021042519551549600_REF12","doi-asserted-by":"crossref","unstructured":"Guo, C., Yang, W. and Lobe, C. G. (2002). A Cre recombinase transgene with mosaic, widespread tamoxifen-inducible action. Genesis32, 8-18.","DOI":"10.1002\/gene.10021"},{"key":"2021042519551549600_REF13","unstructured":"Graham, J. D. and Clarke, C. L. (1997). Physiological action of progesterone in target tissues. Endocr. Rev.18, 502-519."},{"key":"2021042519551549600_REF14","doi-asserted-by":"crossref","unstructured":"Hendrix, E. M., Myatt, L., Sellers, S., Russell, P. T. and Larsen, W. J. (1995). Steroid hormone regulation of rat myometrial gap junction formation: effects on cx43 levels and trafficking. Biol. Reprod.52, 547-560.","DOI":"10.1095\/biolreprod52.3.547"},{"key":"2021042519551549600_REF15","doi-asserted-by":"crossref","unstructured":"Imamura, T., Luedke, C. E., Vogt, S. K. and Muglia, L. J. (2000). Oxytocin modulates the onset of murine parturition by competing ovarian and uterine effects. Am. J. Physiol. Regul. Integr. Comp. Physiol.279, 1061-1067.","DOI":"10.1152\/ajpregu.2000.279.3.R1061"},{"key":"2021042519551549600_REF16","doi-asserted-by":"crossref","unstructured":"Kasten, F. H. (1975). Functional capacity of neonatal mammalian myocardial cells during aging in tissue culture. Adv. Exp. Med. Biol.53, 389-420.","DOI":"10.1007\/978-1-4757-0731-1_34"},{"key":"2021042519551549600_REF17","doi-asserted-by":"crossref","unstructured":"Kilarski, W. M., Dupont, E., Coppen, S., Yeh, H. I., Vozzi, C., Gourdie, R. G., Rezapour, M., Ulmsten, U., Roomans, G. M. and Severs, N. J. (1998). Identification of two further gap-junctional proteins, connexin40 and connexin45, in human myometrial smooth muscle cells at term. Eur. J. Cell Biol.75, 1-8.","DOI":"10.1016\/S0171-9335(98)80040-X"},{"key":"2021042519551549600_REF18","doi-asserted-by":"crossref","unstructured":"Kilarski, W. M., Rothery, S., Roomans, G. M., Ulmsten, U., Rezapour, M., Stevenson, S., Coppen, S. R., Dupont, E. and Severs, N. J. (2001). Multiple connexins localized to individual gap-junctional plaques in human myometrial smooth muscle. Microsc. Res. Tech.54, 114-122.","DOI":"10.1002\/jemt.1126"},{"key":"2021042519551549600_REF19","doi-asserted-by":"crossref","unstructured":"Kretz, M., Maass, K. and Willecke, K. (2004). Expression and function of connexins in the epidermis, studied with transgenic mouse mutants. Eur. J. Cell Biol.83, 647-654.","DOI":"10.1078\/0171-9335-00422"},{"key":"2021042519551549600_REF20","doi-asserted-by":"crossref","unstructured":"Ku\u0308hbandner, S., Brummer, S., Metzger, D., Chambon, P., Hofmann, F. and Feil, R. (2000). Temporally controlled somatic mutagenesis in smooth muscle. Genesis28, 15-22.","DOI":"10.1002\/1526-968X(200009)28:1<15::AID-GENE20>3.0.CO;2-C"},{"key":"2021042519551549600_REF21","doi-asserted-by":"crossref","unstructured":"Kumar, N. M. and Gilula, N. B. (1996). The gap junction communication channel. Cell84, 381-388.","DOI":"10.1016\/S0092-8674(00)81282-9"},{"key":"2021042519551549600_REF22","doi-asserted-by":"crossref","unstructured":"Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227, 680-685.","DOI":"10.1038\/227680a0"},{"key":"2021042519551549600_REF23","doi-asserted-by":"crossref","unstructured":"Le Gurun, S., Martin, D., Formenton, A., Maechler, P., Caille, D., Waeber, G., Meda, P. and Haefliger, J. A. (2003). Connexin-36 contributes to control function of insulin-producing cells. J. Biol. Chem.278, 37690-37697.","DOI":"10.1074\/jbc.M212382200"},{"key":"2021042519551549600_REF24","doi-asserted-by":"crossref","unstructured":"Lye, S. J. (1994). The ionitiation and inhibition of labor-toward a molecular understanding. Semin. Reprod. Endocrinol.12, 284-297.","DOI":"10.1055\/s-2007-1016409"},{"key":"2021042519551549600_REF25","doi-asserted-by":"crossref","unstructured":"Lye, S. J., Nicholson, B. J., Mascarenhas, M., MacKenzie, L. and Petrocelli, T. (1993). Increased expression of connexin-43 in the rat myometrium during labor is associated with an increase in the plasma estrogen:progesterone ratio. Endocrinology132, 2380-2386.","DOI":"10.1210\/endo.132.6.8389279"},{"key":"2021042519551549600_REF26","doi-asserted-by":"crossref","unstructured":"Mitchell, J. A. and Lye, S. J. (2002). Differential expression of activator protein-1 transcription factors in pregnant rat myometrium. Biol. Reprod.67, 240-246.","DOI":"10.1095\/biolreprod67.1.240"},{"key":"2021042519551549600_REF27","doi-asserted-by":"crossref","unstructured":"Orsino, A., Taylor, C. V. amd Lye, S. J. (1996). Connexin-26 and connexin-43 are differentially expressed and regulated in the rat myometrium throughout late pregnancy and with the onset of labor. Endocrinology137, 1545-1553.","DOI":"10.1210\/endo.137.5.8612484"},{"key":"2021042519551549600_REF28","doi-asserted-by":"crossref","unstructured":"Ou, C. W., Orsino, A. and Lye, S. J. (1997). Expression of connexin-43 and connexin-26 in the rat myometrium during pregnancy and labor is differentially regulated by mechanical and hormonal signals. Endocrinology138, 5398-5407.","DOI":"10.1210\/endo.138.12.5624"},{"key":"2021042519551549600_REF29","doi-asserted-by":"crossref","unstructured":"Oviedo-Orta, E. and Howard Evans, W. (2004). Gap junctions and connexin-mediated communication in the immune system. Biochim. Biophys. Acta1662, 102-112.","DOI":"10.1016\/j.bbamem.2003.10.021"},{"key":"2021042519551549600_REF30","doi-asserted-by":"crossref","unstructured":"Palliser, H. K., Ooi, G. T., Hirst, J. J., Rice, G., Dellios, N. L., Escalona, R. M. and Young, I. R. (2004). Changes in the expression of prostaglandin E and F synthases at induced and spontaneous labour onset in the sheep. J. Endocrinol.180, 469-477.","DOI":"10.1677\/joe.0.1800469"},{"key":"2021042519551549600_REF31","doi-asserted-by":"crossref","unstructured":"Pepe, G. J. and Rothchild, I. (1974). A comparative study of serum progesterone levels in pregnancy and in various types of pseudopregnancy in the rat. Endocrinology95, 275-279.","DOI":"10.1210\/endo-95-1-275"},{"key":"2021042519551549600_REF32","doi-asserted-by":"crossref","unstructured":"Piersanti, M. and Lye, S. J. (1995). Increase in messenger ribonucleic acid encoding the myometrial gap junction protein, connexin-43, requires protein synthesis and is associated with increased expression of the activator protein-1, c-fos. Endocrinology136, 3571-3578.","DOI":"10.1210\/endo.136.8.7628395"},{"key":"2021042519551549600_REF33","doi-asserted-by":"crossref","unstructured":"Reaume, A. G., de Sousa, P. A., Kulkarni, S., Langille, B. L., Zhu, D., Davies, T. C., Juneja, S. C., Kidder, G. M. and Rossant, J. (1995). Cardiac malformation in neonatal mice lacking connexin43. Science267, 1831-1834.","DOI":"10.1126\/science.7892609"},{"key":"2021042519551549600_REF34","unstructured":"Reynolds, L. P. and Redmer, D. A. (1999). Growth and development of the corpus luteum. J. Reprod. Fertil.54, 181-191."},{"key":"2021042519551549600_REF35","doi-asserted-by":"crossref","unstructured":"Schwenk, F., Ku\u0308hn, R., Angrand, P. O., Rajewsky, K. and Stewart, A. F. (1998). Temporally and spatially regulated somatic mutagenesis in mice. Nucleic Acids Res.26, 1427-1432.","DOI":"10.1093\/nar\/26.6.1427"},{"key":"2021042519551549600_REF36","doi-asserted-by":"crossref","unstructured":"Seibler, J., Zevnik, B., Kuter-Luks, B., Andreas, S., Kern, H., Hennek, T., Rode, A., Heimann, C., Faust, N., Kauselmann, G. et al. (2003). Rapid generation of inducible mouse mutants. Nucleic Acids Res.31, e12.","DOI":"10.1093\/nar\/gng012"},{"key":"2021042519551549600_REF37","doi-asserted-by":"crossref","unstructured":"Shynlova, O. P., Oldenhof, A. D., Liu, M., Langille, L. and Lye, S. J. (2002). Regulation of c-fos expression by static stretch in rat myometrial smooth muscle cells. Am. J. Obstet. Gynecol.186, 1358-1365.","DOI":"10.1067\/mob.2002.122415"},{"key":"2021042519551549600_REF38","doi-asserted-by":"crossref","unstructured":"So\u0308hl, G., Odermatt, B., Maxeiner, S., Degen, J. and Willecke, K. (2004). New insights into the expression and function of neural connexins with transgenic mouse mutants. Brain Res. Brain Res. Rev.47, 245-259.","DOI":"10.1016\/j.brainresrev.2004.05.006"},{"key":"2021042519551549600_REF39","doi-asserted-by":"crossref","unstructured":"Theis, M., de Wit, C., Schlaeger, T. M., Eckardt, D., Kru\u0308ger, O., Do\u0308ring, B., Risau, W., Deutsch, U., Pohl, U. and Willecke, K. (2001). Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene. Genesis29, 1-13.","DOI":"10.1002\/1526-968X(200101)29:1<1::AID-GENE1000>3.0.CO;2-0"},{"key":"2021042519551549600_REF40","doi-asserted-by":"crossref","unstructured":"van Rijen, H. V., Eckardt, D., Degen, J., Theis, M., Ott, T., Willecke, K., Jongsma, H. J., Opthof, T. and de Bakker, J. M. (2004). Slow conduction and enhanced anisotropy increase the propensity for ventricular tachyarrhythmias in adult mice with induced deletion of connexin43. Circulation109, 1048-1055.","DOI":"10.1161\/01.CIR.0000117402.70689.75"},{"key":"2021042519551549600_REF41","doi-asserted-by":"crossref","unstructured":"Willecke, K., Eiberger, J., Degen, J., Eckardt, D., Romualdi, A., Gu\u0308ldenagel, M., Deutsch, U. and So\u0308hl, G. (2002). Structural and functional diversity of connexin genes in the mouse and human genome. Biol. Chem.383, 725-737.","DOI":"10.1515\/BC.2002.076"},{"key":"2021042519551549600_REF42","doi-asserted-by":"crossref","unstructured":"Yeh, H. I., Dupont, E., Coppen, S., Rothery, S. and Severs, N. J. (1997). Gap junction localization and connexin expression in cytochemically identified endothelial cells of arterial tissue. J. Histochem. Cytochem.45, 539-550.","DOI":"10.1177\/002215549704500406"},{"key":"2021042519551549600_REF43","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wienands, J., Zurn, C. and Reth, M. (1998). Induction of the antigen receptor expression on B lymphocytes results in rapid competence for signaling of SLP-65 and Syk. EMBO J.17, 7304-7310.","DOI":"10.1093\/emboj\/17.24.7304"},{"key":"2021042519551549600_REF44","doi-asserted-by":"crossref","unstructured":"Zingg, H. H., Rozen, F., Chu, K., Larcher, A., Arslan, A., Richard, S. and Lefebvre, D. (1995). Oxytocin and oxytocin receptor gene expression in the uterus. Recent Prog. Horm. Res.50, 255-273.","DOI":"10.1016\/B978-0-12-571150-0.50015-9"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/119\/9\/1715\/1369241\/1715.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/119\/9\/1715\/1369241\/1715.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T16:51:58Z","timestamp":1619369518000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/119\/9\/1715\/29661\/Ablation-of-connexin43-in-uterine-smooth-muscle"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,5,1]]},"references-count":44,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2006,5,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.02892","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1032182.372867","asserted-by":"object"}]},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2006,5,1]]}}}