PATZ1 gene has a critical role in the spermatogenesis and testicular tumours
PATZ1 gene has a critical role in the spermatogenesis and testicular tumours
复制标题
DOI：
10.1002/path.2323
复制
发表时间：
2008-05-01
影响因子：
7.3
通讯作者：
Chieffi, P.
中科院分区：
文献类型：
--
作者：
Fedele, M.;Franco, R.;Chieffi, P.
PATZ1是最近发现的锌指蛋白，由于POZ结构域的存在，它作为一个转录抑制因子影响不同启动子的基础活性。为了深入了解其生物学作用，我们培养了缺乏PATZ1基因的小鼠。雄性PATZ1（-/-）小鼠不能生育，表明该基因在精子发生中起着至关重要的作用。与此一致的是，来自这些小鼠的大多数成年睾丸仅显示少量精母细胞，与细胞凋亡增加有关，精子和精子完全缺失，随后失去管状结构。通过northern blot、western blot和免疫组化对PATZ1的表达进行分析，发现其存在于支持细胞中，而在生殖细胞中，仅存在于精原细胞中。由于PATZ1已被认为是一种潜在的肿瘤抑制基因，我们也研究了它在睾丸生殖细胞（tgct）衍生肿瘤中的表达。尽管PATZ1蛋白在这些肿瘤中的表达增加，但它在细胞质中脱位，表明功能受损。这些结果表明，PATZ1在正常雄性配子体发生中起着至关重要的作用，其上调和错误定位可能与tgct的发育有关。版权所有2008年英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
PATZ1 is a recently discovered zinc finger protein that, due to the presence of the POZ domain, acts as a transcriptional repressor affecting the basal activity of different promoters. To gain insights into its biological role, we generated mice lacking the PATZ1 gene. Male PATZ1(-/-) mice were unfertile, suggesting a crucial role of this gene in spermatogenesis. Consistently, most of adult testes from these mice showed only few spermatocytes, associated with increased apoptosis, and complete absence of spermatids and spermatozoa, with the subsequent loss of tubular structure. The analysis of PATZ1 expression, by northern blot, western blot and immunohistochemistry, revealed its presence in Sertoli cells and, among the germ cells, exclusively in the spermatogonia. Since PATZ1 has been indicated as a potential tumour suppressor gene, we also looked at its expression in tumours deriving from testicular germ cells (TGCTs). Although expression of PATZ1 protein was increased in these tumours, it was delocalized in the cytoplasm, suggesting an impaired function. These results indicate that PATZ1 plays a crucial role in normal male gametogenesis and that its up-regulation and mis-localization could be associated to the development of TGCTs. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.