Veis D J, Sorenson C M, Shutter J R, Korsmeyer S J
Department of Medicine, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110.
Cell. 1993 Oct 22;75(2):229-40. doi: 10.1016/0092-8674(93)80065-m.
bcl-2-/-mice complete embryonic development, but display growth retardation and early mortality postnatally. Hematopoiesis including lymphocyte differentiation is initially normal, but thymus and spleen undergo massive apoptotic involution. Thymocytes require an apoptotic signal to manifest accelerated cell death. Renal failure results from severe polycystic kidney disease characterized by dilated proximal and distal tubular segments and hyperproliferation of epithelium and interstitium. bcl-2-/-mice turn gray with the second hair follicle cycle, implicating a defect in redox-regulated melanin synthesis. The abnormalities in these loss of function mice argue that Bcl-2 is a death repressor molecule functioning in an antioxidant pathway.
bcl-2基因敲除小鼠能够完成胚胎发育，但出生后表现出生长迟缓和早期死亡。包括淋巴细胞分化在内的造血过程最初是正常的，但胸腺和脾脏会经历大规模的凋亡性萎缩。胸腺细胞需要凋亡信号才能表现出加速的细胞死亡。肾衰竭是由严重的多囊肾病导致的，其特征是近端和远端肾小管节段扩张以及上皮和间质的过度增殖。bcl-2基因敲除小鼠在第二个毛囊周期时毛发变灰，这表明氧化还原调节的黑色素合成存在缺陷。这些功能丧失小鼠的异常情况表明，Bcl-2是一种在抗氧化途径中发挥作用的死亡抑制分子。
