MICE WITH REDUCED LEVELS OF P53 PROTEIN EXHIBIT THE TESTICULAR GIANT-CELL DEGENERATIVE SYNDROME
MICE WITH REDUCED LEVELS OF P53 PROTEIN EXHIBIT THE TESTICULAR GIANT-CELL DEGENERATIVE SYNDROME
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DOI：
10.1073/pnas.90.19.9075
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发表时间：
1993-10-01
影响因子：
11.1
通讯作者：
LEVINE, AJ
中科院分区：
文献类型：
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作者：
ROTTER, V;SCHWARTZ, D;LEVINE, AJ
携带p53启动子-氯霉素乙酰转移酶（CAT）转基因的转基因小鼠被发现主要在睾丸中抑制CAT酶活性。内源性p53 mRNA和蛋白水平低于非转基因对照小鼠。各种p53启动子-CAT转基因小鼠在其睾丸中表现出多核巨细胞，这是一种退行性综合征，可能是由于四倍体初级精母细胞无法完成减数分裂所致。在一些纯合子p53基因缺失小鼠的遗传品系中也观察到巨细胞变性综合征。鉴于p53在DNA修复机制中起作用的假设，推测p53在精子发生的减数分裂粗线期特异性表达的生理功能是允许有足够的时间进行DNA重组和修复事件，这些事件发生在该阶段以适当地完成。具有降低的p53水平的初级精母细胞可能在DNA修复方面受损，从而导致不成熟的遗传缺陷巨细胞的发育。
Transgenic mice which carry hybrid p53 promoter-chloramphenicol acetyltransferase (CAT) transgenes were found to ''press CAT enzymatic activity predominantly in the testes. Endogenous levels of p53 mRNA and protein were lower than in the nontransgenic control mice. The various p53 promoter-CAT transgenic mice exhibited in their testes multinucleated giant cells, a degenerative syndrome resulting presumably from the inability of the tetraploid primary spermatocytes to complete meiotic division. The giant-cell degenerative syndrome was also observed in some genetic strains of homozygous p53 null mice. In view of the hypothesis that p53 plays a role in DNA repair mechanisms, it is tempting to speculate that the physiological function of p53 that is specifically expressed in the meiotic pachytene phase of spermatogenesis is to allow adequate time for the DNA reshuffling and repair events which occur at this phase to be properly completed. Primary spermatocytes which have reduced p53 levels are probably impaired with respect to DNA repair, thus leading to the development of genetically defective giant cells that do not mature.