We showed that the Id3 gene was efficiently disrupted in early thymocyte development prior to T cell receptor (TCR)-mediated positive selection.
An LckCre transgene was used to induce Id3 deletion in developing T cells. In order to gain a better understanding of individual cell types in this disease model, we generated an Id3 conditional allele.
Both B and T lymphocytes have been implicated to contribute to the disease phenotype in this disease model. Id3 deficient mice develop autoimmune disease similar to human Sjögren’s syndrome. The Id3 gene has been shown to play important roles in the development and function of broad tissue types including B and T cells. Our observation provides an experimental case that autoimmune disease may be induced by acquired mutation in developing T cells. This study establishes a new model for investigating the relationship between T cell development and autoimmune disease. This progressive feature of disease development is very similar to those observed in Id3 germline knockout mice. These mice developed exocrinopathy starting at two months of age and subsequently exhibited high incidence of lymphocyte infiltration to salivary glands between eight and 12 months of age. Consequently, thymocyte maturation was impaired in the conditional knockout mice. Id3 deficient mice develop autoimmune disease similar to human Sjögren's syndrome.