Defective Lymphoid Development in Mice Lacking Jak3

TLDR

Jak3, a Janus kinase mainly expressed in hematopoietic cells, signals exclusively through the common γ chain of IL‑2, IL‑4, IL‑7, IL‑9, and IL‑15 receptors, whereas Jak1, Jak2, and Tyk2 are broadly expressed. Homozygous Jak3 knockout mice were generated by gene targeting. Jak3‑deficient mice displayed profound thymocyte loss, severe B‑cell and T‑cell lymphopenia resembling SCID, and the remaining lymphocytes were functionally deficient, underscoring Jak3’s essential role in γ‑c signaling and lymphoid development.

Abstract

The Janus tyrosine kinases (Jaks) play a central role in signaling through cytokine receptors. Although Jak1, Jak2, and Tyk2 are widely expressed, Jak3 is predominantly expressed in hematopoietic cells and is known to associate only with the common γ (γ c ) chain of the interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15 receptors. Homozygous mutant mice in which the Jak3 gene had been disrupted were generated by gene targeting. Jak3-deficient mice had profound reductions in thymocytes and severe B cell and T cell lymphopenia similar to severe combined immunodeficiency disease (SCID), and the residual T cells and B cells were functionally deficient. Thus, Jak3 plays a critical role in γ c signaling and lymphoid development.