Mark Flapan Award

Elizabeth P. Blankenhorn, Ph.D.
Drexel University College of Medicine, Philadelphia, Pa.

"Genes That Regulate the Scleroderma Trait in Mice"

Scleroderma is a serious and complex inflammatory disease. One mouse model, Tsk2, has many features of the human disease, including tight skin, dysregulated extracellular matrix deposition, and significant autoimmunity with age. The gene for Tsk2 mice is still unidentified; and genes that interact with Tsk2 are also completely unknown. We propose to identify both the Tsk2 gene and genes that affect how Tsk2.

We collected data on a large population of mice with scleroderma signs, and have bred them to an unusual mouse strain that has an extra copy of a receptor (TLR7) that could enhance clinical disease. Our preliminary results are encouraging. We have also developed a more accurate measurement of scleroderma‐like skin
thickening, and we have noted a significant effect of sex and age on the Tsk2 trait. We narrowed the Tsk2/+ genetic interval, and it now contains only ~25 known genes, which makes our search much easier.

In the new proposal, we will map the gene that causes tight skin and autoimmunity in Tsk2/+ mice, test the effect of deleting TLR7 from the mouse genome, and breed the line to a common congenic background for further study of this gene.