A novel mouse model carrying a gene trap insertion into the Hmgxb4 gene locus to examine Hmgxb4 expression in vivo

  • Physiol Rep. 2024 Apr;12(8):e16014. doi: 10.14814/phy2.16014.
Liang Wang  1  2 ,  Xiangqin He  2 ,  Guoqing Hu  2 ,  Jinhua Liu  2  3 ,  Xiuhua Kang  2  3 ,  Luyi Yu  2  3 ,  Kunzhe Dong  2 ,  Juanjuan Zhao  2 ,  Aizhen Zhang  4  5 ,  Wei Zhang  3 ,  Michael W Brands  6 ,  Huabo Su  2  4 ,  Zeqi Zheng  1 ,  Jiliang Zhou  2
Affiliations
  • 1. Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 2. Department of Pharmacology & Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
  • 3. Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 4. Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
  • 5. Training Center, Guangxi Medical College, Nanning, China.
  • 6. Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA.
Abstract

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.

Keywords
Hmgxb4; arterial injury; gene expression; gene trap; β‐galactosidase activity.