Defects in regulation of apoptosis in caspase-2-deficient mice
Defects in regulation of apoptosis in caspase-2-deficient mice
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DOI：
10.1101/gad.12.9.1304
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发表时间：
1998-05-01
影响因子：
10.5
通讯作者：
Yuan, JY
中科院分区：
文献类型：
--
作者：
Bergeron, L;Perez, GI;Yuan, JY
在胚胎发育过程中，大量细胞自然死亡以形成新的生物体。蛋白酶的半胱天冬酶家族的成员是必需的细胞内死亡效应物。在此，我们产生了caspase-2缺陷小鼠，以评估这种酶在细胞凋亡的各种范例的要求。突变小鼠的卵巢中具有过量的生殖细胞，并且发现卵母细胞对暴露于化疗药物后的细胞死亡具有抗性。颗粒酶B和穿孔素介导的凋亡在caspase-2缺陷的B淋巴母细胞中是缺陷的。相反，在caspase-2缺陷小鼠中，发育过程中运动神经元的细胞死亡加速。此外，caspase-2缺陷的交感神经元比野生型神经元更有效地进行细胞凋亡时，剥夺了神经生长因子。因此，胱天蛋白酶-2作为一个积极和消极的细胞死亡效应，这取决于细胞谱系和发展阶段。
During embryonic development, a large number of cells die naturally to shape the new organism. Members of the caspase family of proteases are essential intracellular death effecters. Herein, we generated caspase-2-deficient mice to evaluate the requirement for this enzyme in various paradigms of apoptosis. Excess numbers of germ cells were endowed in ovaries of mutant mice and the oocytes were found to be resistant to cell death following exposure to chemotherapeutic drugs. Apoptosis mediated by granzyme B and perforin was defective in caspase-2-deficient B lymphoblasts. In contrast, cell death of motor neurons during development was accelerated in caspase-2-deficient mice. In addition, caspase-2-deficient sympathetic neurons underwent apoptosis more effectively than wild-type neurons when deprived of NGF. Thus, caspase-2 acts both as a positive and negative cell death effector, depending upon cell lineage and stage of development.