ArticleHuman molecular genetics2008
The conditional connexin43G138R mouse mutant represents a new model of hereditary oculodentodigital dysplasia in humans.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 161 citations in OpenAlex.
- Skeletal abnormalities caused by a Connexin43Bone research · 2025Article
- Genetically engineered human embryonic kidney cells as a novel vehicle for dual patch clamp study of human gap junction channels.The Biochemical journal · 2024Article
- Targeting NANOG and FAK via Cx26-derived Cell-penetrating Peptides in Triple-negative Breast Cancer.Molecular cancer therapeutics · 2024Article
- Role of Cx43 on the Bone Cell Generation, Function, and Survival.Bioelectricity · 2023Article
- Article
- Connexin hemichannels as candidate targets for cardioprotective and anti-arrhythmic treatments.The Journal of clinical investigation · 2023Review
- Somatic GJA4 gain-of-function mutation in orbital cavernous venous malformations.Angiogenesis · 2023Article
- Connexin 43 hemichannels and prostaglandin EFrontiers in cell and developmental biology · 2023Review
- 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
- Genetic determinants of syndactyly: perspectives on pathogenesis and diagnosis.Orphanet journal of rare diseases · 2022Review
- Connexin Mutations and Hereditary Diseases.International journal of molecular sciences · 2022Review
- Review
- Generation and Characterization of an Inducible Cx43 Overexpression System in Mouse Embryonic Stem Cells.Cells · 2022Article
- Cellular mechanisms of connexin-based inherited diseases.Trends in cell biology · 2022Review
- Differential Domain Distribution of gnomAD- and Disease-Linked Connexin Missense Variants.International journal of molecular sciences · 2021Article
- Connexins in the Heart: Regulation, Function and Involvement in Cardiac Disease.International journal of molecular sciences · 2021Review
- Astrocytic Connexin43 Channels as Candidate Targets in Epilepsy Treatment.Biomolecules · 2020Review
- Article
- The Role of Connexin Channels in the Response of Mechanical Loading and Unloading of Bone.International journal of molecular sciences · 2020Review
- Connexin 43 Mutations Lead to Increased Hemichannel Functionality in Skin Disease.International journal of molecular sciences · 2019Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Oculodentodigital dysplasia (ODDD) is a dominant negatively inherited disorder with variable but characteristic anomalies of the fingers and toes, eyes, face and teeth, which are caused by mutations in the connexin 43 (Cx43) gene. All mutations analyzed so far have a negative influence on the conductance through gap junctional channels and hemichannels, as well as trafficking of Cx43 protein in transfected cells. In this study, we inserted the human Cx43G138R point mutation into the mouse Cx43 gene and generated mice conditionally expressing this mutation. All ODDD phenotypic manifestations observed in humans, including syndactyly and enamel hypoplasia as well as craniofacial, bone and heart anomalies, were also observed with significant penetrance in Cx43G138R mice. When this mutation was specifically expressed in cardiomyocytes, characteristic alterations in the electrocardiogram and spontaneous arrhythmias were recorded. In vitro studies with Cx43G138R-expressing cells revealed loss of the Cx43 P2 phosphorylation state, which was also absent in the mutated hearts. This loss has previously been associated with gap junctional dysfunction and increased cellular ATP release. The Cx43G138R mutated mice show significantly increased arrhythmogeneity ex vivo in Langendorff experiments with explanted hearts and in vivo in particular under hypoxic conditions. Our results suggest that the increased activity of ATP-releasing channels in Cx43G138R mutated cardiomyocytes may further reduce the already decreased gap junctional communication and thus aggravate arrhythmogenesis in the mouse mutant.
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Registered trials
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