Gpr26-KO Mouse

GPR26, an orphan G-protein-coupled receptor (GPCR), is mainly expressed in the brain and has multiple functions. It is involved in regulating various biological processes such as energy homeostasis, emotion regulation, and may play a role in inflammatory responses and tumorigenesis [2,4,5,6]. Genetic models, especially knockout mouse models, have been crucial in studying its functions.

GPR26-deficient mice show increased anxiety-and depression-like behaviors, accompanied by reduced phosphorylated cyclic AMP responsive element-binding protein (pCREB) levels in the central amygdala, indicating its importance in emotion regulation [5]. Targeted inactivation of GPR26 in mice leads to hyperphagia and adiposity by activating AMP-activated protein kinase (AMPK) in the hypothalamus, suggesting its role in energy homeostasis [6]. In addition, knockdown of GPR26 in human monocytes enhances monocyte ROS production, MAPK signaling, pro-inflammatory activation, adhesion to endothelial cells, and Caspase 3 activity, showing its protective role against hyperglycemia-mediated monocyte activation [1]. In cancer-related studies, high expression levels and constitutive activity of GPR26 in liver cancer cells are associated with antitumor activity, and in glioblastoma, GPR26 is downregulated and is a target gene of miR-188-3p, which may contribute to glioblastoma therapy [2,3].

In summary, GPR26 is a key regulator in emotion regulation, energy homeostasis, and inflammatory responses, as well as having potential implications in cancer. Mouse models, especially GPR26 knockout models, have significantly contributed to understanding its roles in these disease-related areas, providing a basis for further research on its mechanisms and potential therapeutic applications.

References:

1. Kichi, Zahra Abedi, Natarelli, Lucia, Sadeghian, Saeed, Behmanesh, Mehrdad, Weber, Christian. 2022. Orphan GPR26 Counteracts Early Phases of Hyperglycemia-Mediated Monocyte Activation and Is Suppressed in Diabetic Patients. In Biomedicines, 10, . doi:10.3390/biomedicines10071736. https://pubmed.ncbi.nlm.nih.gov/35885041/

2. Liu, Fang, Yang, Wei, Hu, Minghui, Brosius, Juergen, Deng, Cheng. 2021. Constitutive activity of GPR26 regulated by ubiquitin-dependent degradation and its antitumor role. In The FEBS journal, 288, 4655-4682. doi:10.1111/febs.15763. https://pubmed.ncbi.nlm.nih.gov/33577134/

3. Meng, Lei, Jiang, Yuan-Pei, Zhu, Jie, Li, Bo. 2020. MiR-188-3p/GPR26 modulation functions as a potential regulator in manipulating glioma cell properties. In Neurological research, 42, 222-227. doi:10.1080/01616412.2020.1723298. https://pubmed.ncbi.nlm.nih.gov/32024457/

4. Watkins, Lyndsay R, Orlandi, Cesare. 2020. Orphan G Protein Coupled Receptors in Affective Disorders. In Genes, 11, . doi:10.3390/genes11060694. https://pubmed.ncbi.nlm.nih.gov/32599826/

5. Zhang, L-L, Wang, J-J, Liu, Y, Fei, J, Wang, Z-G. 2011. GPR26-deficient mice display increased anxiety- and depression-like behaviors accompanied by reduced phosphorylated cyclic AMP responsive element-binding protein level in central amygdala. In Neuroscience, 196, 203-14. doi:10.1016/j.neuroscience.2011.08.069. https://pubmed.ncbi.nlm.nih.gov/21924326/

6. Chen, Daohong, Liu, Xiaolei, Zhang, Weiping, Shi, Yuguang. 2012. Targeted inactivation of GPR26 leads to hyperphagia and adiposity by activating AMPK in the hypothalamus. In PloS one, 7, e40764. doi:10.1371/journal.pone.0040764. https://pubmed.ncbi.nlm.nih.gov/22815809/