Department of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
J Zhejiang Univ Sci B. 2013 Mar;14(3):171-7. doi: 10.1631/jzus.B1200357.
Testicular nuclear receptor 4 (TR4), also known as NR2C2 (nuclear receptor subfamily 2, group C, member 2), is a transcriptional factor and a member of the nuclear receptor family. TR4 was initially cloned from human and rat hypothalamus, prostate, and testes libraries. For almost two decades, its specific tissue distribution, genomic organization, and chromosomal assignment have been well investigated in humans and animals. However, it has been very difficult to study TR4's physiological functions due to a lack of specific ligands. Gene knock-out animal techniques provide an alternative approach for defining the biological functions of TR4. In vivo studies of TR4 gene knockout mice (TR4(-/-)) found that they display severe spinal curvature, subfertility, premature aging, and prostate prostatic intraepithelial neoplasia (PIN) development. Upstream modulators, downstream target gene regulation, feedback mechanisms, and differential modulation mediated by the recruitment of other nuclear receptors and coregulators have been identified in studies using the TR4(-/-) phenotype. With the establishment of a tissue-specific TR4(-/-) mouse model, research on TR4 will be more convenient in the future.
睾丸核受体 4（TR4），也称为 NR2C2（核受体亚家族 2，C 组，成员 2），是一种转录因子，也是核受体家族的成员。TR4 最初从人类和大鼠下丘脑、前列腺和睾丸文库中克隆得到。近二十年来，其在人类和动物中的特定组织分布、基因组组织和染色体定位已得到很好的研究。然而，由于缺乏特异性配体，TR4 的生理功能研究一直非常困难。基因敲除动物技术为定义 TR4 的生物学功能提供了一种替代方法。TR4 基因敲除小鼠（TR4（-/-））的体内研究发现，它们表现出严重的脊柱弯曲、生育能力下降、早衰和前列腺上皮内瘤形成（PIN）发展。在使用 TR4（-/-）表型的研究中，已经确定了上游调节剂、下游靶基因调控、反馈机制以及通过招募其他核受体和共激活剂进行的差异调节。随着组织特异性 TR4（-/-）小鼠模型的建立，未来对 TR4 的研究将更加方便。
