Marty M S, Singh N P, Holsapple M P, Gollapudi B B
Health and Environmental Research Laboratories, The Dow Chemical Company, 1803 Building, Midland, MI 48674, USA.
Mutat Res. 1999 Jun 1;427(1):39-45. doi: 10.1016/S0027-5107(99)00083-4.
The influence of p53 gene zygosity on select parameters of mouse sperm was investigated by employing knock-out animal models. The background incidence of sperm shape abnormalities, total sperm count, and DNA double strand breaks were determined in p53 nullizygous (-/-) and heterozygous (+/-) mice and these estimates were compared to the corresponding measures in p53 wild-type (+/+) and the inbred C57Bl6 mouse strains. There were no qualitative differences in the incidence of sperm shape abnormalities and sperm counts regardless of p53 zygosity. However, the number of DNA double strand breaks, as measured by the comet assay, were significantly lower in the p53 knock-out mice. This apparent decrease was interpreted to be the result of a possible change in DNA-protein and/or DNA-DNA cross-linking in the germ cells of the knock-out mice. These data show that there is no evidence of increased incidence of gross alterations in spermatogenesis (no significant loss in sperm production nor any increase in the proportion of abnormal sperm produced) in knock-out mice deficient or absent in p53 protein; however, there appear to be changes at the genomic level where the degree of cross-linking was apparently elevated in DNA from p53 nullizygous and heterozygous mice.
通过使用基因敲除动物模型，研究了p53基因纯合性对小鼠精子某些参数的影响。测定了p53基因纯合缺失（-/-）和杂合（+/-）小鼠精子形态异常的背景发生率、精子总数和DNA双链断裂情况，并将这些估计值与p53野生型（+/+）和近交C57Bl6小鼠品系的相应测量值进行比较。无论p53基因的纯合性如何，精子形态异常发生率和精子数量均无质的差异。然而，通过彗星试验测量，p53基因敲除小鼠的DNA双链断裂数量显著降低。这种明显的减少被解释为基因敲除小鼠生殖细胞中DNA-蛋白质和/或DNA-DNA交联可能发生变化的结果。这些数据表明，在缺乏p53蛋白的基因敲除小鼠中，没有证据表明精子发生过程中总体改变的发生率增加（精子产生没有显著损失，也没有异常精子产生比例的任何增加）；然而，在基因组水平上似乎存在变化，p53基因纯合缺失和杂合小鼠的DNA交联程度明显升高。
