Wang Liang, He Xiangqin, Hu Guoqing, Liu Jinhua, Kang Xiuhua, Yu Luyi, Dong Kunzhe, Zhao Juanjuan, Zhang Aizhen, Zhang Wei, Brands Michael W, Su Huabo, Zheng Zeqi, Zhou Jiliang
Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Pharmacology & Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
Physiol Rep. 2024 Apr;12(8):e16014. doi: 10.14814/phy2.16014.
HMG (high mobility group) proteins are a diverse family of nonhistone chromosomal proteins that interact with DNA and a wide range of transcriptional regulators to regulate the structural architecture of DNA. HMGXB4 (also known as HMG2L1) is an HMG protein family member that contains a single HMG box domain. Our previous studies have demonstrated that HMGXB4 suppresses smooth muscle differentiation and exacerbates endotoxemia by promoting a systemic inflammatory response in mice. However, the expression of Hmgxb4 in vivo has not fully examined. Herein, we generated a mouse model that harbors a gene trap in the form of a lacZ gene insertion into the Hmgxb4 gene. This mouse enables the visualization of endogenous HMGXB4 expression in different tissues via staining for the β-galactosidase activity of LacZ which is under the control of the endogenous Hmgxb4 gene promoter. We found that HMGXB4 is widely expressed in mouse tissues and is a nuclear protein. Furthermore, the Hmgxb4 gene trap mice exhibit normal cardiac function and blood pressure. Measurement of β-galactosidase activity in the Hmgxb4 gene trap mice demonstrated that the arterial injury significantly induces Hmgxb4 expression. In summary, the Hmgxb4 gene trap reporter mouse described here provides a valuable tool to examine the expression level of endogenous Hmgxb4 in both physiological and pathological settings in vivo.
高迁移率族（HMG）蛋白是一类多样的非组蛋白染色体蛋白，它们与DNA以及多种转录调节因子相互作用，以调控DNA的结构架构。HMGXB4（也称为HMG2L1）是HMG蛋白家族的成员，含有单个HMG盒结构域。我们之前的研究表明，HMGXB4通过促进小鼠的全身炎症反应来抑制平滑肌分化并加重内毒素血症。然而，Hmgxb4在体内的表达尚未得到充分研究。在此，我们构建了一个小鼠模型，该模型在Hmgxb4基因中插入了一个以lacZ基因形式存在的基因陷阱。通过对内源Hmgxb4基因启动子控制下的LacZ的β-半乳糖苷酶活性进行染色，该小鼠能够在不同组织中可视化内源性HMGXB4的表达。我们发现HMGXB4在小鼠组织中广泛表达，并且是一种核蛋白。此外，Hmgxb4基因陷阱小鼠表现出正常的心脏功能和血压。对Hmgxb4基因陷阱小鼠中β-半乳糖苷酶活性的测量表明，动脉损伤显著诱导Hmgxb4表达。总之，本文所述的Hmgxb4基因陷阱报告小鼠为在体内生理和病理环境下检测内源性Hmgxb4的表达水平提供了一个有价值的工具。
