p53蛋白在周期调节蛋白A1变异引起的雄性小鼠生殖细胞凋亡中的作用

为研究p5 3蛋白在周期调节蛋白A1(cyclinA1)变异引起的雄性小鼠生殖细胞凋亡中的作用 ,以p5 3基因敲除的小鼠和周期调节蛋白A1基因敲除的小鼠杂交 ,获取同胎生单基因变异和双基因同时变异的雄性后代共 4组 12只 .比较它们的性腺和生殖细胞发育 ,并用TUNEL染色法观察和比较生殖细胞的凋亡情况 .在睾丸最大横切面上观察到 :周期调节蛋白A1变异组凋亡细胞最多 (348± 10 4个 ) ,明显高于p5 3 周期调节蛋白A1双基因变异组 (12 1± 38个 ) ,t=3 2 5 79,P =0 0 4 72 .p5 3变异组凋亡细胞最少 (45± 2 4个 ) ,配对t检验显示有非常显著性差异 ,t=8 4 0 13,P =0 0 0 35 .这一研究结果提示 ,p5 3基因可能在雄性生殖细胞的发育中起监视作用 ,并在周期调节蛋白A1变异引起发育异常时启动p5 3途径造成异常细胞的凋亡 .

Role of p53 in Male Germ Cell Apoptosis Induced by Mutant CyclinA1 in Mouse

To study the role of p53 in the male germ cell apoptosis induced by mutant cyclinA1, p53 mutant mice and cyclinA1 mutant mice were crossed to generate 4 groups of male littermates with different genetic background, p53 mutant, cyclinA1 mutant and double mutant. The development and apoptosis of male germ cells were analyzed by TUNEL staining. On the largest cross section of testes, cyclinA1 mutant group presented 348±104 apoptotic cells, which was obviously higher than 121±38, that of double mutant group, t=3.2579,P=0.0472. p53 mutant group presented the least, 45±24 apoptotic cells. Matched pair t-test showed very significant difference, t=8.4013,P=0.0035. This study suggests that p53 mediates male germ cell apoptosis. The p53-dependent apoptosis pathway may be an effector of cellular proofreading that acts to maintain the cellular integrity of germ cells during spermatogenesis.