GLP-1: A novel zinc finger protein required in somatic cells of the gonad for germ cell development
GLP-1: A novel zinc finger protein required in somatic cells of the gonad for germ cell development
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DOI：
10.1016/j.ydbio.2006.07.048
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发表时间：
2007-01-01
影响因子：
2.7
通讯作者：
Morrisey, Edward E.
中科院分区：
文献类型：
--
作者：
Li, Shanru;Lu, Min Min;Morrisey, Edward E.
小鼠性腺发育受多种转录因子调控。在这里，我们报告了一种新的核锌指蛋白称为加塔样蛋白-1（GLP-1），这是在高水平表达的体细胞发育性腺，包括睾丸间质细胞和卵巢颗粒细胞的鉴定和表征。GLP-1的生化分析表明，它作为加塔因子功能的转录抑制因子。为了确定GLP-1在性腺发育中的必要性，通过用细菌lacZ基因替换所有编码外显子来产生小鼠中的无效等位基因。GLP-1（lacz）敲除小鼠存活，内脏器官发育无可检测到的缺陷;然而，雄性和雌性小鼠均完全不育。GLP-1缺失导致雄性精子发育缺陷，早在出生后第1周就观察到成熟精子细胞显著减少。在雌性动物中，早在E17.5，GLP-1缺失就导致生殖细胞发育严重阻滞。总之，这些数据将GLP-1确定为生殖细胞发育所需的性腺体细胞中的关键核阻遏物，并强调了体细胞-生殖细胞相互作用在调控这一关键过程中的重要性。(c)2006爱思唯尔公司All rights reserved.
Mouse gonadal development is regulated by a variety of transcription factors. Here we report the identification and characterization of a novel nuclear zinc finger protein called GATA like protein-1 (GLP-1), which is expressed at high levels in the somatic cells of the developing gonads, including Leydig cells in the testes and granulosa cells in the ovaries. Biochemical analysis of GLP-1 shows that it acts as a transcriptional repressor of GATA factor function. To determine the necessity of GLP-1 in gonadal development, a null allele in mice was generated by replacing all of the coding exons with the bacterial lacZ gene. GLP-1(lacz) null mice are viable with no detectable defects in visceral organ development; however, both males and females are completely infertile. Loss of GLP-1 leads to defective sperm development in males with a marked reduction in mature spermatids observed as early as postnatal week 1. In females, loss of GLP-1 leads to a severe block in germ cell development as early as E17.5. Together, these data identify GLP-1 as a critical nuclear repressor in somatic cells of the gonad that is required for germ cell development, and highlight the importance of somatic-germ cell interactions in the regulation of this critical process. (c) 2006 Elsevier Inc. All rights reserved.