SC35 plays a role in T cell development and alternative splicing of CD45

Molecular diversity via alternative splicing is important for cellular func tion and development. SR proteins are strong candidate regulators of altern ative splicing because they can modulate splice site selection. However, en dogenous substrates for SR proteins are largely unknown, and their roles as splicing regulators in vertebrate development are unclear. Here we report that Cre-mediated conditional deletion of the prototypical SR protein SC35 in the thymus causes a defect in T cell maturation. Deletion of SC35 alters alternative splicing of CD45, a receptor tyrosine phosphatase known to be regulated by differential splicing during thymocyte development and activat ion. This study establishes a model to address the function of SR proteins in physiological settings and reveals a critical role of SC35 in a T cell-s pecific regulated splicing pathway.