Aqp7-KO Mouse

Aqp7, an aquaglyceroporin, is a transmembrane protein that facilitates the transport of glycerol and water across cell membranes [1,2,3,4,5,6,7,8]. It is involved in key metabolic pathways, such as the metabolism of carbohydrates and lipids, and plays a significant role in maintaining normal physiological functions related to adipose tissue, liver, heart, and kidney [1,3,5,6]. Gene knockout mouse models have been valuable in studying Aqp7's functions [6].

In Aqp7 knockout mice, the water permeability of the proximal straight tubule brush border membrane was reduced, and they showed marked glyceroluria, identifying a novel glycerol reabsorption pathway in the proximal straight tubules. Also, AQP1/AQP7 double knockout mice had reduced urinary concentrating ability compared to AQP1 solo knockout mice, indicating Aqp7's substantial contribution to water reabsorption in the proximal straight tubules [6]. In cardiomyocyte-specific Aqp7 deficiency mice, the myocardial infarct size and apoptosis increased in response to ischemia, suggesting that Aqp7-mediated glycerol metabolism helps prevent myocardial ischemia-related damage [5].

In conclusion, Aqp7 is essential for glycerol and water transport, participating in multiple metabolic processes. The Aqp7 knockout mouse models have revealed its role in maintaining kidney function and protecting the heart from ischemic damage, contributing to our understanding of related physiological and pathological mechanisms.

References:

1. Chen, Luting, Chen, Huixi, Liu, Xinmei, Jin, Li, Huang, Hefeng. 2020. AQP7 mediates post-menopausal lipogenesis in adipocytes through FSH-induced transcriptional crosstalk with AP-1 sites. In Reproductive biomedicine online, 41, 1122-1132. doi:10.1016/j.rbmo.2020.08.008. https://pubmed.ncbi.nlm.nih.gov/33132060/

2. Falato, Michael, Chan, Ruth, Chen, Liao Y. 2022. Aquaglyceroporin AQP7's affinity for its substrate glycerol: Have we reached convergence in the computed values of glycerol-aquaglyceroporin affinity? In RSC advances, 12, 3128-3135. doi:10.1039/d1ra07367b. https://pubmed.ncbi.nlm.nih.gov/35222995/

3. Lebeck, Janne. 2014. Metabolic impact of the glycerol channels AQP7 and AQP9 in adipose tissue and liver. In Journal of molecular endocrinology, 52, R165-78. doi:10.1530/JME-13-0268. https://pubmed.ncbi.nlm.nih.gov/24463099/

4. Zhang, Li, Yao, Deqiang, Xia, Ying, Zhou, Lu, Cao, Yu. 2020. The structural basis for glycerol permeation by human AQP7. In Science bulletin, 66, 1550-1558. doi:10.1016/j.scib.2020.12.006. https://pubmed.ncbi.nlm.nih.gov/36654284/

5. Ishihama, Sohta, Yoshida, Satoya, Yoshida, Tatsuya, Murohara, Toyoaki, Takefuji, Mikito. . LPL/AQP7/GPD2 promotes glycerol metabolism under hypoxia and prevents cardiac dysfunction during ischemia. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35, e22048. doi:10.1096/fj.202100882R. https://pubmed.ncbi.nlm.nih.gov/34807469/

6. Sohara, Eisei, Rai, Tatemitsu, Sasaki, Sei, Uchida, Shinichi. 2006. Physiological roles of AQP7 in the kidney: Lessons from AQP7 knockout mice. In Biochimica et biophysica acta, 1758, 1106-10. doi:. https://pubmed.ncbi.nlm.nih.gov/16860289/

7. Huang, Peng, Venskutonytė, Raminta, Prasad, Rashmi B, Artner, Isabella, Lindkvist-Petersson, Karin. 2023. Cryo-EM structure supports a role of AQP7 as a junction protein. In Nature communications, 14, 600. doi:10.1038/s41467-023-36272-y. https://pubmed.ncbi.nlm.nih.gov/36737436/

8. Lebeck, Janne, Søndergaard, Esben, Nielsen, Søren. 2018. Increased AQP7 abundance in skeletal muscle from obese men with type 2 diabetes. In American journal of physiology. Endocrinology and metabolism, 315, E367-E373. doi:10.1152/ajpendo.00468.2017. https://pubmed.ncbi.nlm.nih.gov/29783856/