ArticleBiology of reproduction2009
A dominant loss-of-function GJA1 (Cx43) mutant impairs parturition in the mouse.
Article in Biology of reproduction, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- SOX4 exerts contrasting regulatory effects on labor-associated gene promoters in myometrial cells.PloS one · 2024Article
- MYB and ELF3 differentially modulate labor-inducing gene expression in myometrial cells.PloS one · 2023Article
- Proteomic and miRNA Profiles of Exosomes Derived from Myometrial Tissue in Laboring Women.International journal of molecular sciences · 2022Article
- Towards a Better Understanding of Genotype-Phenotype Correlations and Therapeutic Targets for Cardiocutaneous Genes: The Importance of Functional Studies above Prediction.International journal of molecular sciences · 2022Review
- Human Chorionic Gonadotropin Modulates the Transcriptome of the Myometrium and Cervix in Late Gestation.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
- The pregnant myometrium is epigenetically activated at contractility-driving gene loci prior to the onset of labor in mice.PLoS biology · 2020Article
- Functional Hierarchy of Uterotonics Required for Successful Parturition in Mice.Endocrinology · 2019Article
- Connexin 43 maintains tissue polarity and regulates mitotic spindle orientation in the breast epithelium.Journal of cell science · 2019Article
- The interplay between electrical and chemical synaptogenesis.Journal of neurophysiology · 2018Review
- Maternal obesity-induced decreases in plasma, hepatic and uterine polyunsaturated fatty acids during labour is reversed through improved nutrition at conception.Scientific reports · 2018Article
- Article
- Intra-amniotic Ureaplasma parvum-Induced Maternal and Fetal Inflammation and Immune Responses in Rhesus Macaques.The Journal of infectious diseases · 2016Article
- Molecular evidence of functional progesterone withdrawal in human myometrium.Nature communications · 2016Article
- Uterine endoplasmic reticulum stress-unfolded protein response regulation of gestational length is caspase-3 and -7-dependent.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Physiological roles of connexins and pannexins in reproductive organs.Cellular and molecular life sciences : CMLS · 2015Review
- Asymmetric expression of connexins between luminal epithelial- and myoepithelial- cells is essential for contractile function of the mammary gland.Developmental biology · 2015Article
- Neutrophil recruitment and activation in decidua with intra-amniotic IL-1beta in the preterm rhesus macaque.Biology of reproduction · 2015Article
- Alterations in gap junction connexin43/connexin45 ratio mediate a transition from quiescence to excitation in a mathematical model of the myometrium.Journal of the Royal Society, Interface · 2014Article
- TGFBR1 is required for mouse myometrial development.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Transforming growth factor β signaling in uterine development and function.Journal of animal science and biotechnology · 2014Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expression of GJA1 (commonly known as connexin43 or Cx43), a major myometrial gap junction protein, is upregulated before the onset of delivery, suggesting an essential role for Cx43-mediated gap junctional intercellular communication (GJIC) in normal uterine contraction during parturition. To determine how a disease-linked Cx43 mutation affects myometrial function, we studied a mutant mouse model carrying an autosomal dominant mutation (Gja1(Jrt)) in the gene encoding Cx43 that displays features of the human genetic disease oculodentodigital dysplasia. We found that Cx43 level, specifically the phosphorylated species of the protein, is significantly reduced in the myometrium of the mutant mice (Gja1(Jrt)/+), as revealed by Western blotting and immunostaining. Patch-clamp electrophysiological measurements demonstrated that coupling between myometrial smooth muscle cells is reduced to <15% of wild-type, indicating that the mutant protein acts dominantly on its wild-type counterpart. The phosphorylated species of Cx43 in the mutant myometrium failed to increase prior to parturition as well as in response to exogenous estrogen. Correspondingly, in vitro experiments with uterine strips revealed weaker contraction of the mutant myometrium and reduced responsiveness to oxytocin, providing an explanation for the prolonged gestation and presence of suffocated fetuses in the uteri that were observed in some of the mutant mice. We conclude that the Gja1(Jrt) mutation has a dominant-negative effect on Cx43 function in the myometrium, severely reducing GJIC, leading to impaired parturition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.