Specific functional pathologies of Cx43 mutations associated with oculodentodigital dysplasia

John J. Kelly, Jessica L. Esseltine, Qing Shao, Ethylin Wang Jabs, Jacinda Sampson, Mari Auranen, Donglin Bai, Dale W. Laird

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Oculodentodigital dysplasia (ODDD) is a rare genetic disease that affects the development of multiple organs in the human body. More than 70 mutations in the gap junction connexin43 (Cx43) gene, GJA1, are associated with ODDD, most of which are inherited in an autosomal dominant manner. Many patients exhibit similar clinical presentations. However, there is high intrafamilial and interfamilial phenotypic variability. To better understand this variability, we established primary human dermal fibroblast cultures from several ODDD patients and unaffected controls. In the present study, we characterized three fibroblast lines expressing heterozygous p.L7V, p.G138R, and p.G143S Cx43 variants. All ODDD fibroblasts exhibited slower growth, reduced migration, and defective cell polarization, traits common to all ODDD fibroblasts studied so far. However, we found striking differences in overall expression levels, with p.L7V down-regulated at the mRNA and protein level. Although all of the Cx43 variants could traffic to the cell surface, there were stark differences in gap junction plaque formation, gap junctional intercellular communication, Cx43 phosphorylation, and hemichannel activity among Cx43 variants, as well as subtle differences in myofibroblast differentiation. Together these findings enabled us to discover mutation-specific pathologies that may help to predict future clinical outcomes.

Original languageEnglish (US)
Pages (from-to)2172-2185
Number of pages14
JournalMolecular Biology of the Cell
Issue number14
StatePublished - Jul 15 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Specific functional pathologies of Cx43 mutations associated with oculodentodigital dysplasia'. Together they form a unique fingerprint.

Cite this