Maurice van Steensel, MD PhD
Michel van Geel, MD, University Hospital Maastricht

Drs. van Geel and van Steensel

Keratitis-Ichthyosis-Deafness (KID) syndrome is a rare genetic disease characterized by severe ichthyosis, keratitis (inflammation of the cornea) leading to blindness and deafness. People with KID syndrome are also more sensitive to skin infections and can even develop skin cancer. This severe disease is caused by mutations in the protein connexin26, which is part of specialized communication channels between cells called gap junctions. After several years of research, we know that mutations in connexin26 can cause a range skin disorders, some similar to KID syndrome but most quite distinct. The reason for this diversity is not understood because we have a very limited view of what gap junctions do in the skin. As a consequence, we have no good treatment for our patients. In addition, it is difficult to study gap junction disorders of the skin because they are so rare. To remedy this situation, we decided to develop a mouse model for KID syndrome. To do this, we transfer a human connexin26 gene with a KID syndrome mutation into mouse embryo cells. Because we are interested in the ichthyosis that patients with KID syndrome develop, we use modern transgene technology to make a mouse that develops skin abnormalities but not the keratitis or the deafness. We also make sure that the disease gene is inducible, which means that it only becomes manifest when the animal is given an antibiotic. This approach reduces animal discomfort. Because we can switch the disease gene on and off at will, we can examine whether the skin disease is reversible. If it is, that means that patients might benefit from cutting-edge treatments that prevent the mutant protein from being made. Finally, we have constructed the transgene is such a way, that we can easily exchange the disease gene for another one so that we, or other groups, may study other types of ichthyosis.

We are excited that the FIRST is funding the development of our mouse model and we have begun the process of making mutant embryos. If all goes well, we will soon have a versatile model in which to study a severe form of ichthyosis and its treatment.

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