OXGR1, also known as 2-oxoglutarate receptor 1, is a G-protein-coupled receptor (GPCR). It plays a crucial role in various biological processes, participating in metabolic regulation, immune response, and ion transport pathways. OXGR1 is associated with pathways like the PI3K/AKT pathway, and its ligands such as itaconate (ITA) and α-ketoglutaric acid (AKG) are involved in initiating downstream signaling events, which are of great biological importance. Genetic models, especially KO mouse models, have been valuable in studying its function [1-9].

In KO mouse models, OXGR1 knockout leads to skeletal muscle atrophy, decreased capillary density, and endurance exercise capacity, indicating its role in skeletal muscle blood flow and metabolism [2]. In the male reproductive system, OXGR1 knockout and knockdown models show that it is essential for epididymal sperm maturation and fluid acid-base balance [3]. In Goldblatt hypertensive mice, OXGR1-dependent (pro)renin receptor upregulation in the collecting ducts of the clipped kidney affects sodium balance and blood pressure [4].

In conclusion, OXGR1 is vital for multiple biological functions including muscle development, male fertility, and renal sodium balance. The use of KO mouse models has significantly contributed to understanding its role in these processes and related disease conditions such as nephrolithiasis and hypertension, providing insights into potential therapeutic targets [1,4].

References:

1. Majmundar, Amar J, Widmeier, Eugen, Heneghan, John F, Alper, Seth L, Hildebrandt, Friedhelm. 2022. OXGR1 is a candidate disease gene for human calcium oxalate nephrolithiasis. In Genetics in medicine : official journal of the American College of Medical Genetics, 25, 100351. doi:10.1016/j.gim.2022.11.019. https://pubmed.ncbi.nlm.nih.gov/36571463/

2. Yang, Jinping, Xu, Guli, Xu, Yiming, Jiang, Qingyan, Shu, Gang. 2022. AKG/OXGR1 promotes skeletal muscle blood flow and metabolism by relaxing vascular smooth muscle. In Life metabolism, 1, 285-297. doi:10.1093/lifemeta/loac026. https://pubmed.ncbi.nlm.nih.gov/39872069/

3. Xu, Chang, Yuan, Yexian, Zhang, Cha, Jiang, Qingyan, Shu, Gang. 2022. Smooth muscle AKG/OXGR1 signaling regulates epididymal fluid acid-base balance and sperm maturation. In Life metabolism, 1, 67-80. doi:10.1093/lifemeta/loac012. https://pubmed.ncbi.nlm.nih.gov/39872683/

4. Cárdenas, Pilar, Nuñez-Allimant, Camila, Silva, Katherin, Prieto, Minolfa C, Gonzalez, Alexis A. 2024. OXGR1-Dependent (Pro)Renin Receptor Upregulation in Collecting Ducts of the Clipped Kidney Contributes to Na+ Balance in Goldblatt Hypertensive Mice. In International journal of molecular sciences, 25, . doi:10.3390/ijms251810045. https://pubmed.ncbi.nlm.nih.gov/39337535/