Panx1, or pannexin 1, is a ubiquitously expressed protein that forms an ATP-releasing membrane channel. It plays significant roles in multiple biological processes including inflammation, blood pressure regulation, and is involved in pathways related to energy metabolism, immune cell recruitment, and cell-cell communication [1,2,4,5]. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, have been crucial for studying Panx1's functions.

In cardiomyocytes, Panx1-deficient mice (Panx1MyHC6) showed increased glycolytic metabolism and protection against cardiac hypertrophy in non-ischemic heart failure, likely due to reduced immune cell recruitment [1]. In the liver, hepatic Panx1 knockdown or global knockout in mice led to disturbed glucolipid metabolism, indicating its role in maintaining hepatic glucolipid homeostasis [2]. In the nervous system, global or neuron-specific Panx1 deletion in mice decreased pain thresholds in inflammatory pain models, with neuron-specific deletion also reducing neuronal differentiation and excitability [4]. Panx1-null mice also had deficits in long-term spatial reference memory, suggesting the involvement of both astrocyte and neuronal Panx1 in memory consolidation [5].

In conclusion, Panx1 is essential for various biological functions, including energy metabolism, immune response, pain sensitivity, and memory. The use of Panx1 KO/CKO mouse models has significantly contributed to understanding its roles in heart failure, hepatic metabolism, inflammatory pain, and memory-related diseases, providing insights into potential therapeutic strategies for these conditions.

References:

1. Pavelec, Caitlin M, Young, Alexander P, Luviano, Hannah L, Wolf, Matthew J, Leitinger, Norbert. 2024. Cardiomyocyte PANX1 Controls Glycolysis and Neutrophil Recruitment in Hypertrophy. In Circulation research, 135, 503-517. doi:10.1161/CIRCRESAHA.124.324650. https://pubmed.ncbi.nlm.nih.gov/38957990/

2. Hu, Cheng-Qing, Hou, Tao, Xiang, Rui, Chi, Yu-Jing, Yang, Ji-Chun. 2024. PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis. In Military Medical Research, 11, 41. doi:10.1186/s40779-024-00543-6. https://pubmed.ncbi.nlm.nih.gov/38937853/

3. Bisht, Kanchan, Okojie, Kenneth A, Sharma, Kaushik, Kuan, Chia-Yi, Eyo, Ukpong B. 2021. Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice. In Nature communications, 12, 5289. doi:10.1038/s41467-021-25590-8. https://pubmed.ncbi.nlm.nih.gov/34489419/

4. Xing, Qu, Cibelli, Antonio, Yang, Greta Luyuan, Guan, Fang-Xia, Spray, David C. 2024. Neuronal Panx1 drives peripheral sensitization in experimental plantar inflammatory pain. In Military Medical Research, 11, 27. doi:10.1186/s40779-024-00525-8. https://pubmed.ncbi.nlm.nih.gov/38685116/

5. Obot, Price, Subah, Galadu, Schonwald, Antonia, Stanton, Patric K, Scemes, Eliana. . Astrocyte and Neuronal Panx1 Support Long-Term Reference Memory in Mice. In ASN neuro, 15, 17590914231184712. doi:10.1177/17590914231184712. https://pubmed.ncbi.nlm.nih.gov/37365910/