A New Mouse Model of Sjogren's Syndrome
Background: Sjogren's Syndrome is a grave autoimmune disease in which destruction of the exocrine glands leads to severe dryness of the eyes and mouth, with additional systemic complications. The pathogenesis of Sjogren's Syndrome is unclear, and treatment options are limited. Development of good animal models of the disease might lead to effective treatments for human patients, as well as a greater understanding of the cellular and molecular alterations that underlie disease progression. Technology: We have established a novel mouse model of primary Sjogren's Syndrome (as opposed to secondary Sjogren's Syndrome, in which the disease occurs in conjunction with other autoimmune disorders). Our data indicate that the disease is driven by aberrant T lymphocytes. In this model, the signaling enzyme phosphoinositide 3-kinase (PI3K) is selectively ablated in thymocytes and T cells. This model is superior to other models for the following reasons. First, all animals develop symptoms within 6-8 months, particularly leukocyte infiltrates into the lacrimal glands. Other models do not show such early or complete penetrance. Second, the disease is similar to primary Sjogren's Syndrome in humans in that other autoimmune sequelae are not usually observed. Other models commonly studied, including the MRL / lpr and NOD strains, are characterized by more generalized autoimmunity. Application: The mouse model can used for (I) studying mechanisms of disease development in Sjogren's Syndrome; (2) testing of therapies for treatment and/or prevention of Sjogren's Syndrome.
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