DEFECTIVE LYMPHOID DEVELOPMENT IN MICE LACKING JAK3

The Janus tyrosine kinases (Jaks) play a central role in signaling thr ough cytokine receptors. Although Jak1, Jak2, and Tyk2 are widely expr essed, Jak3 is predominantly expressed in hematopoietic cells and is k nown to associate only with the common gamma (gamma(c)) chain of the i nterleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15 receptors. Homozygous m utant mice in which the Jak3 gene had been disrupted were generated by gene targeting. Jak3-deficient mice had profound reductions in thymoc ytes and severe B cell and T cell lymphopenia similar to severe combin ed immunodeficiency disease (SCID), and the residual T cells and B cel ls were functionally deficient. Thus, Jak3 plays a critical role in ga mma(c) signaling and lymphoid development.