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The Reaper-Binding Protein Scythe Modulates Apoptosis and Proliferation during Mammalian Development

Department of Genetics and Tumor Cell Biology,¹ Animal Resource Center, St. Jude Children's Research Hospital, Memphis, Tennessee 38105²

Received 5 June 2005/ Returned for modification 28 July 2005/ Accepted 16 September 2005

Scythe (BAT3 [HLA-B-associated transcript 3]) is a nuclear protein that has been implicated in apoptosis, as it can modulate Reaper, a central apoptotic regulator in Drosophila melanogaster. While Scythe can markedly affect Reaper-dependent apoptosis in Xenopus laevis cell extracts, the function of Scythe in mammals is unknown. Here, we report that inactivation of Scythe in the mouse results in lethality associated with pronounced developmental defects in the lung, kidney, and brain. In all cases, these developmental defects were associated with dysregulation of apoptosis and cellular proliferation. Scythe^–/– cells were also more resistant to apoptosis induced by menadione and thapsigargin. These data show that Scythe is critical for viability and normal development, probably via regulation of programmed cell death and cellular proliferation.

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