The wst gene regulates multiple forms of thymocyte apoptosis.

Mice homozygous for the autosomal recessive mutation Wasted (wst/wst) display a disease characterized by immunodeficiency, cerebellar dysfunction, and sensitivity of their hematopoeitic cells to gamma radiation. Wasted mice die by 30 days of age. In this report, we show that the Wasted thymus shows evidence of dramatically increased apoptosis in situ. Moreover, wst/wst thymocytes are more sensitive to apoptosis induced by gamma radiation, heat shock, alpha-CD3 stimulation, and dexamethasone treatment in vitro. Thus, wst gene is a regulator of thymocyte apoptosis both in vitro and in vivo. The elevated levels of thymocyte apoptosis may be a major contributor to the lymphoid dysfunction and ultimate death in wst/wst mice.