Skin healing in overdrive

The NIH is reporting on the role of connexin 26 in psoriasis and eczema (via Science Blog):

To test whether a defective skin barrier can actually produce these diseases, a team of NIH researchers focused on a specific gene called connexin 26, which makes a protein that forms connections between skin cells that create the normal barrier. When the skin is intact, the production of connexin 26 is turned off once there is enough to hook all the skin cells together. When skin is damaged by a cut or a scrape, connexin 26 is produced while new skin cells reproduce and heal the wound. Researchers have shown that connexin 26 production is turned on in the sore skin of people with psoriasis, but it wasn't clear what role connexin 26 played in the disorder.
To determine connexin 26's role in psoriasis, NIH researchers created a line of transgenic mice that over-produce connexin 26. The resulting mice develop psoriatic-type skin sores, just like humans with psoriasis.

They spin this into a story about how creating a skin barrier with a special lotion might be able to eliminate the autoimmune response. That would certainly be useful, and the part about the connexin 26 mutant rats that get the psoriasis sores is very interesting.

But there is more to this story -- connexin 26 is an essential protein in gap junctions, which are direct conduits allowing molecules to move between cells. It is most well known in association with congenital deafness. Kenneson et al. (2002) review the function of the gene relative to hearing loss:

The Gap Junction Beta 2 or GJB2 gene (GenBank M86849, OMIM: *121011) resides at the chromosomal location 13q11 and encodes for the protein connexin 26, a beta class gap junction protein expressed in the cochlea and in the epidermis. Connexin 26 hexamers form channels between cells that, when open, allow cell-to-cell diffusion of small molecules. This function is necessary for recycling potassium in the cochlea that plays a critical role in sensorineural hearing function. The GJB2 gene is small, with the entire coding region of 680 base pairs falling within exon 2.

Gap junctions are everywhere in the body. The 26 in connexin 26 denotes its molecular weight; other connexins with different molecular weights also help form gap junctions. Connexin 26 in particular has been studied for functional variation in uterine tissue, placenta, and the nervous system.

There are many high-frequency allelic variants in different human populations. Cochran et al. (2006) examine one allele common in Ashkenazi Jews and speculate that it has a role in disease resistance. That may be true of several of the common alleles, or there may be other functional roles under selection.

References:

Kenneson A, Van Naarden Braun K, Boyle C. 2002. GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: A HuGE review. Genet in Med 4:258-274. DOI link

Cochran G, Hardy J, Harpending H. 2006. Natural history of Ashkenazi intelligence. J Biosoc Sci (in press). DOI link