Ace2-KO Mouse

Ace2, short for Angiotensin converting enzyme 2, is a transmembrane glycoprotein and a key part of the renin-angiotensin system (RAS) [1,2,3,4,7]. It functions to convert AngiotensinⅡ (AngⅡ) to Angiotensin1-7 (A1-7), and the formed ACE2/A1-7/Mas axis counteracts vasoconstriction, the inflammatory response, oxidative stress, and cell proliferation, thus negatively regulating RAS [3]. Ace2 also helps transport amino acids across the membrane and is widely expressed in multiple tissues like lungs, cardiovascular system, gastrointestinal tract, etc. [1,3]. Its study through genetic models like KO/CKO mouse models can potentially reveal more about its functions and roles in diseases.

In the context of COVID-19, Ace2 is the receptor of SARS-COV-2, mediating viral entry into cells [1,2,4,5,6,7,8]. Some studies suggest that down-regulation of Ace2 due to viral binding may lead to angiotensin imbalance, immune dysregulation, and endothelial cell dysfunction [4]. Also, soluble Ace2 (sAce2) formed by its shedding from the membrane can act as the receptor of SARS-COV-2, and elevated concentrations of sAce2 are more related to the disease [1]. Regarding other diseases, Ace2 is down-regulated in diabetes, hypertension, or lung injury, while SARS-COV-2 upregulates Ace2 levels, enhancing host cell susceptibility to virus infection [2]. Ace2 also plays a role in glucose homeostasis and insulin secretion by regulating beta cell physiology in the pancreas, indicating a possible link between SARS-COV-2 and diabetes [6]. Moreover, Ace2 polymorphisms have significant linkages with various diseases, including the severity of SARS-COV-2 infection [8].

In conclusion, Ace2 is a crucial regulator in the RAS, involved in maintaining homeostasis, transporting amino acids, and playing a role in multiple physiological processes. Through model-based research, its significance in diseases such as COVID-19, diabetes, hypertension, and lung injury has been revealed. Understanding Ace2's functions and regulations can potentially provide new strategies for treating these diseases.

References:

1. Wang, Jieqiong, Zhao, Huiying, An, Youzhong. 2022. ACE2 Shedding and the Role in COVID-19. In Frontiers in cellular and infection microbiology, 11, 789180. doi:10.3389/fcimb.2021.789180. https://pubmed.ncbi.nlm.nih.gov/35096642/

2. Wang, Chia-Wen, Chuang, Huai-Chia, Tan, Tse-Hua. 2023. ACE2 in chronic disease and COVID-19: gene regulation and post-translational modification. In Journal of biomedical science, 30, 71. doi:10.1186/s12929-023-00965-9. https://pubmed.ncbi.nlm.nih.gov/37608279/

3. Li, Rui, Li, Fangyu, Yuan, Li. . ACE2 Regulates Glycolipid Metabolism in Multiple Tissues. In Frontiers in bioscience (Landmark edition), 29, 17. doi:10.31083/j.fbl2901017. https://pubmed.ncbi.nlm.nih.gov/38287822/

4. Cook, Joshua R, Ausiello, John. 2021. Functional ACE2 deficiency leading to angiotensin imbalance in the pathophysiology of COVID-19. In Reviews in endocrine & metabolic disorders, 23, 151-170. doi:10.1007/s11154-021-09663-z. https://pubmed.ncbi.nlm.nih.gov/34195965/

5. Jia, Hongpeng, Neptune, Enid, Cui, Honggang. . Targeting ACE2 for COVID-19 Therapy: Opportunities and Challenges. In American journal of respiratory cell and molecular biology, 64, 416-425. doi:10.1165/rcmb.2020-0322PS. https://pubmed.ncbi.nlm.nih.gov/33296619/

6. Memon, Bushra, Abdelalim, Essam M. 2021. ACE2 function in the pancreatic islet: Implications for relationship between SARS-CoV-2 and diabetes. In Acta physiologica (Oxford, England), 233, e13733. doi:10.1111/apha.13733. https://pubmed.ncbi.nlm.nih.gov/34561952/

7. Beacon, Tasnim H, Delcuve, Geneviève P, Davie, James R. 2020. Epigenetic regulation of ACE2, the receptor of the SARS-CoV-2 virus1. In Genome, 64, 386-399. doi:10.1139/gen-2020-0124. https://pubmed.ncbi.nlm.nih.gov/33086021/

8. Singh, HariOm, Choudhari, Ranjana, Nema, Vijay, Khan, Abdul Arif. 2020. ACE2 and TMPRSS2 polymorphisms in various diseases with special reference to its impact on COVID-19 disease. In Microbial pathogenesis, 150, 104621. doi:10.1016/j.micpath.2020.104621. https://pubmed.ncbi.nlm.nih.gov/33278516/