Cellular mechanisms of mutant connexins in skin disease and hearing loss

Cell Commun Adhes. Jul-Dec 2003;10(4-6):347-51. doi: 10.1080/cac.10.4-6.347.351.


It has been demonstrated that distinct germline mutations within four connexin (Cx) genes, Cx26, Cx30, Cx31, and Cx30.3, underlie hearing loss and/or epidermal disease. Here, we describe two Cx26 mutations associated with skin disease. With the goal of understanding the mechanism(s) of Cx-associated human disease and how different mutations within the same Cx protein can result in different disorders, we performed a number of functional analyses investigating the cellular effects of disease-associated Cx mutations in keratinocytes and other cell types. Epidermal disease-associated proteins studied were primarily cytoplasmic with limited trafficking ability. FACS analysis of WT and mutant EGFP-Cx31 transfected keratinocytes revealed a high percentage of cell death associated with the skin disease-associated mutant Cx31 proteins.

MeSH terms

  • Cells, Cultured
  • Connexin 26
  • Connexins / genetics
  • Connexins / metabolism*
  • Gap Junctions / genetics
  • Gap Junctions / metabolism*
  • Green Fluorescent Proteins
  • Hearing Loss / genetics
  • Humans
  • Keratinocytes / metabolism*
  • Luminescent Proteins / metabolism
  • Mutation
  • Skin Diseases / genetics*


  • Connexins
  • DFNA3 protein, human
  • Luminescent Proteins
  • Connexin 26
  • GJB3 protein, human
  • Green Fluorescent Proteins