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 dysfun ction, 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 si tu. Moreover, wst/wst thymocytes are more sensitive to apoptosis induc ed by gamma radiation, heat shock, alpha-CD3 stimulation, and dexameth asone treatment in vitro. Thus, wst gene is a regulator of thymocyte a poptosis both in vitro and in vivo. The elevated levels of thymocyte a poptosis may be a major contributor to the lymphoid dysfunction and ul timate death in wst/wst mice. (C) 1998 Academic Press.