Testicular wild-type p53 expression in transgenic mice induces spermiogenesis alterations ranging from differentiation defects to apoptosis
Testicular wild-type p53 expression in transgenic mice induces spermiogenesis alterations ranging from differentiation defects to apoptosis
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DOI：
10.1038/sj.onc.1203052
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发表时间：
1999-11-11
期刊：
影响因子：
8
通讯作者：
May, E
中科院分区：
文献类型：
--
作者：
Allemand, I;Anglo, A;May, E
虽然p53在发育过程中起重要作用，但过量的p53对胚胎发生和细胞分化具有显著的影响。在试图分析体内p53活性的影响，我们已经产生了转基因小鼠表达野生型p53的金属硫蛋白I启动子的控制下。在所建立的三个转基因株系中，外源性p53在转基因雄性的减数分裂后细胞中组成型表达，两个株系为低生育力。表达较高水平p53的转基因雄性产生很少的精子，因为大多数发育中的精子细胞经历凋亡。在表现出中等量p53的低生育力雄性中，畸形精子是明显的，这表明减数分裂后细胞的终末分化改变。相反，低水平的p53并不导致第三系不育。这些结果表明，体内p53的活性依赖于细胞内存在的p53的量，正如已经在体外证明的那样。
While p53 is dispensable for development, an excess of p53 has dramatic consequences on the embryogenesis and on the cell differentiation. In an attempt to analyse in vivo the effects of p53 activity, we have generated transgenic mice expressing the wild-type p53 under the control of the metallothionein I promoter. In the three transgenic lines established, exogenous p53 is expressed constitutively in the postmeiotic cells of transgenic males and two lines are subfertile, Transgenic males expressing the upper level of p53 produce few spermatozoa since the majority of developing spermatids undergo apoptosis, In the subfertile males exhibiting an intermediate amount of p53, teratozoospermia is obvious suggesting an altered terminal differentiation of postmeiotic cells. In contrast lower level of p53 does not lead the third line to sterility. These results suggest that the activity of p53 is dependent irt vivo on the amount of p53 present within cells, as it has been already demonstrated in vitro.