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Patz1 基因纯合敲除小鼠的胚胎缺陷和生长改变。

Embryonic defects and growth alteration in mice with homozygous disruption of the Patz1 gene.

机构信息

Istituto di Endocrinologia ed Oncologia Sperimentale del CNR and Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Naples, Italy.

出版信息

J Cell Physiol. 2013 Mar;228(3):646-53. doi: 10.1002/jcp.24174.

DOI:10.1002/jcp.24174
PMID:22886576
Abstract

PATZ1 is an emerging cancer-related gene coding for a POZ/AT-hook/kruppel Zinc finger transcription factor, which is lost or misexpressed in human neoplasias. Here, we investigated its role in development exploring wild-type and Patz1-knockout mice during embryogenesis. We report that the Patz1 gene is ubiquitously expressed at early stages of development and becomes more restricted at later stages, with high levels of expression in actively proliferating neuroblasts belonging to the ventricular zones of the central nervous system (CNS). The analysis of embryos in which Patz1 was disrupted revealed the presence of severe defects in the CNS and in the cardiac outflow tract, which eventually lead to a pre-mature in utero death during late gestation or soon after birth. Moreover, the Patz1-null mice showed a general growth retardation, which was consistent with the slower growth rate and the increased susceptibility to senescence of Patz1(-/-) mouse embryonic fibroblasts (MEFs) compared to wild-type controls. Therefore, these results indicate a critical role of PATZ1 in the control of cell growth and embryonic development.

摘要

PATZ1 是一种新兴的与癌症相关的基因,编码 POZ/AT 钩/kruppel 锌指转录因子,该基因在人类肿瘤中丢失或表达异常。在这里,我们通过研究野生型和 Patz1 敲除小鼠在胚胎发生过程中的作用来探索其在发育中的作用。我们报告称,Patz1 基因在发育的早期阶段广泛表达,在后期阶段变得更加受限,在属于中枢神经系统 (CNS) 室区的活跃增殖神经母细胞中表达水平较高。对 Patz1 被破坏的胚胎进行分析表明,CNS 和心脏流出道存在严重缺陷,最终导致妊娠晚期或出生后不久的宫内死亡。此外,Patz1 缺失小鼠表现出普遍的生长迟缓,这与 Patz1(-/-) 小鼠胚胎成纤维细胞 (MEF) 相比野生型对照具有较慢的生长速度和更高的衰老易感性一致。因此,这些结果表明 PATZ1 在控制细胞生长和胚胎发育中起着关键作用。

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