Protein Overexpression Underlies Inflammatory Skin Diseases

Researchers working with a line of genetically engineered mice found that a mutation that triggers over-production of the skin protein connexin 26 caused defects in the protective properties of the skin, which resulted in inflammatory skin diseases such as eczema and psoriasis.

Investigators at the [U.S.] National Institutes of Health (Bethesda, MD, USA) genetically engineered a line of mice that did not express the gene for the transcription factor Kruppel-like factor 4 (Klf4). These animals displayed severe defects in skin development as well as overexpression of the of the gap junction protein connexin 26 (Cx26). This protein is required by the embryo during development and by mature individuals during wound healing but is otherwise inactive.

The current work, which was published in the May 2006 issue of the Journal of Clinical Investigation, showed that constant activation of Cx26 interfered with skin development in young animals and skin maintenance and healing in older ones. Skin conditions resembling human eczema and psoriasis appeared due to infiltration of the skin by hyperactive immune cells.

"Hopefully, this will help us understand the complex genetics of psoriasis,” said senior author Dr. Julia A. Segre, an investigator at the National Institutes of Health. "Previous genetic studies have focused on the genes that regulate immune response. We are now examining the effect of genes that are involved in both regulating the growth of skin cells and signaling to the immune cells. The skin cells grow so fast that they fail to make a normal barrier, and the body is stimulating the immune response because of material (chemicals and allergens) coming through the barrier.”



Related Links:
[U.S.] National Institutes of Health