Specialised Function Revealed by Connexin Mutation

Human Mutations

Gap junctions have a lengthy ancestral history in metazoans, thus it is not surprising that they have been modified to perform a wide range of physiological tasks in many cell types. Human mutations and targeted connexin gene deletion in mice have revealed numerous cell- and tissue-specific activities of GJIC. In humans, mutations in Cx47 cause Pelizaeus-Merzbacher-Like-Disease, a central demyelinating disease, and mutations in Cx32 cause X-linked Charcot-Marie-Tooth syndrome, a common peripheral demyelination neuropathy. Mutations in Cx26 cause more than half of all profound hereditary deafness; these illnesses are frequently syndromic and involve skin conditions. Disorders of the epidermis and the auditory system also accompany mutations in Cx31 and Cx30, though they are often less severe. Mutations in the ocular lens-specific genes Cx46 or Cx50, whose expression is primarily localised to the lens of the eye, are frequently linked to familial cataracts. The pleomorphic, syndromic disorder oculodentodigital dysplasia, which affects a variety of cell types, is caused by mutations in the Cx43 gene.

Targeted Mutations in Mice

Targeted connexin mutations in mice have shown a wide range of gap-junction functions in different organs. In many of these situations, a specific connexin fills a specific void, performing a crucial task that cannot be covered by another connexin. For instance, the Cx26 deletion causes the gap junction-coupled syncytiotrophoblast I and II in the labyrinth layer of the placenta to stop transporting glucose, which causes embryonic lethality. The human placenta, in contrast, has a single enormous syncytiotrophoblast and is hence immune to Cx26 mutations. Cx45 deletions are also embryonically fatal; in this example, a cardiac arrhythmia probably occurred just as the heart started to beat. Due to a failure in ovarian follicle formation at the antral stage, Cx37 knockouts are female sterile. A premature restart of meiosis and luteinization is thought to be caused by a lack of connection between the cumulus cells and the oocyte. Heart arrhythmias resembling human right-bundle-branch block are caused by the loss of Cx40, which is common in the His-Purkinje system.

In three different mouse lines, the Cx43 coding sequence was changed to one of the Cx32, Cx40, or Cx26 coding regions. The three connexins were not able to replace Cx43 in all situations, as evidenced by the fact that all three animal lines displayed novel functional abnormalities specific to each connexin. A knockin of Cx31 into the Cx43 locus revealed the pulmonary outflow deficits reported in the Cx43KO animal, despite none of the lines exhibiting the deficiencies. Connexins may therefore perform both distinct and redundant tasks.

The fundamental structural and operational unit of all living things is the cell. Each cell has a cytoplasm that is surrounded by a membrane and is home to a variety of biomolecules, including proteins and nucleic acids.

Cells can develop specialised functions and perform a variety of tasks within the cell, including protein synthesis, DNA repair, replication, and motility. Within the cell, cells can specialise and move around. Due to their small size, the majority of cells are measured in micrometres.