BCL-2-DEFICIENT MICE DEMONSTRATE FULMINANT LYMPHOID APOPTOSIS, POLYCYSTIC KIDNEYS, AND HYPOPIGMENTED HAIR

bcl-2 -/- mice complete embryonic development, but display growth reta rdation and early mortality postnatally. Hematopoiesis including lymph ocyte differentiation is initially normal, but thymus and spleen under go massive apoptotic involution. Thymocytes require an apoptotic signa l to manifest accelerated cell death. Renal failure results from sever e polycystic kidney disease characterized by dilated proximal and dist al tubular segments and hyperproliferation of epithelium and interstit ium. bcl-2 -/- mice turn gray with the second hair follicle cycle, imp licating a defect in redox-regulated melanin synthesis. The abnormalit ies in these loss of function mice argue that Bcl-2 is a death repress or molecule functioning in an antioxidant pathway.