Gap junctions in health and disease

Gap junctions are communicating junctions that consist of hexameric proteins called connexins and mediate the exchange of low molecular weight metabolites and ions between cells in contact. It has long been hypothesized that gap junctional intercellular communication plays a crucial role in the maintenance of homeostasis, morphogenesis, cell differentiation, and growth control in multicellular organisms. Recent discoveries of human genetic disorders associated with mutations in connexin genes and experimental data on connexin knockout mice have provided direct evidence of this. Connexin 32 mutations cause X-linked Charcot-Marie-Tooth disease, an inherited peripheral demyelinating neuropathy. Connexin 26 mutations have been found in hereditary nonsyndromic sensorineural deafness. Connexin 43 knockout mice die shortly after delivery because of cardiac malformation. Connexin 32 knockout mice show high incidences of spontaneous and chemically induced liver tumors, and develop a late-onset progressive peripheral neuropathy analogous to human Charcot-Marie-Tooth disease. Female connexin 37 knockout mice are infertile as the result of abnormalities in ovarian follicular growth, control of luteinization, and oocyte maturation. Connexin 46 knockout mice develop nuclear cataracts. Further identification of connexin mutations in other human diseases and generation of mice with modified connexin genes will aid our understanding of the biology of gap junctions. © The Clinical Electron Microscopy Society of Japan 1998.