Bpgm-KO Mouse

Bpgm, short for bisphosphoglycerate mutase, is expressed in human erythrocytes and is responsible for the production of 2,3-bisphosphoglycerate (2,3-DPG), which plays a crucial role in modulating oxygen affinity to hemoglobin [1,2,3,4]. It is also involved in pathways related to glycolysis and metabolic reprogramming, thus having overall biological importance in processes like hypoxia response and energy regulation. Genetic models such as KO/CKO mouse models can be valuable for further exploring its functions.

In a mouse model, erythrocyte-specific deficiency in equilibrative nucleoside transporter 1 (eEnt1-/-) abolishes the activation of Bpgm, leading to reduced 2,3-bisphosphoglycerate and glutathione, overwhelming oxidative stress, and severe renal hypoxia, indicating its role in protecting against renal hypoxia and CKD progression [2]. In another study, inducible knockout of Bpgm in a tubular-specific, doxycycline-inducible Bpgm-knockout mouse model resulted in rapid kidney injury within 4 days, characterized by proximal tubular damage and tubulointerstitial fibrosis. Proteomic analyses revealed its involvement in key metabolic pathways, including glycolysis, oxidative stress response, and inflammation [4].

In summary, Bpgm is essential for the production of 2,3-DPG and is involved in multiple metabolic pathways. Studies using KO/CKO mouse models have revealed its critical role in maintaining kidney function and protecting against renal hypoxia-related diseases such as CKD [2,4].

References:

1. E, Guoji, Sun, Binda, Liu, Bao, Gao, Yuqi, Zhang, Erlong. 2022. Enhanced BPGM/2,3-DPG pathway activity suppresses glycolysis in hypoxic astrocytes via FIH-1 and TET2. In Brain research bulletin, 192, 36-46. doi:10.1016/j.brainresbull.2022.11.002. https://pubmed.ncbi.nlm.nih.gov/36334804/

2. Chen, Changhan, Xie, TingTing, Zhang, Yujin, D'Alessandro, Angelo, Xia, Yang. 2023. Erythrocyte ENT1-AMPD3 Axis is an Essential Purinergic Hypoxia Sensor and Energy Regulator Combating CKD in a Mouse Model. In Journal of the American Society of Nephrology : JASN, 34, 1647-1671. doi:10.1681/ASN.0000000000000195. https://pubmed.ncbi.nlm.nih.gov/37725437/

3. Qiang, Qingfen, Manalo, Jeanne M, Sun, Hong, D'Alessandro, Angelo, Xia, Yang. 2021. Erythrocyte adenosine A2B receptor prevents cognitive and auditory dysfunction by promoting hypoxic and metabolic reprogramming. In PLoS biology, 19, e3001239. doi:10.1371/journal.pbio.3001239. https://pubmed.ncbi.nlm.nih.gov/34138843/

4. Kulow, Vera A, Roegner, Kameliya, Labes, Robert, Rosenberger, Christian, Fähling, Michael. 2024. Beyond hemoglobin: Critical role of 2,3-bisphosphoglycerate mutase in kidney function and injury. In Acta physiologica (Oxford, England), 241, e14242. doi:10.1111/apha.14242. https://pubmed.ncbi.nlm.nih.gov/39422260/