Slc22a7-KO Mouse

Slc22a7, also known as organic anion transporter 2 (OAT2), is a member of the solute carrier superfamily. It functions as a facilitative transporter for various substances such as cyclic nucleotides (like cGMP), nicotinic acid, creatinine, and uric acid [4,5,7,8]. It is involved in lipid metabolism through insulin, PI3K-Akt, MAPK, AMPK, mTOR, and PPAR signaling pathways [2]. It may also play a role in the renal handling of uric acid as a step in tubular secretion and could potentially regulate serum uric acid levels [6].

In a study on diabetic kidney disease (DKD) in mice, the mRNA expression level of Slc22a7 was declined in the kidney tissues of DKD mice compared with control mice, suggesting its involvement in lipid metabolism and the PPAR signaling pathway in DKD [1]. In Chinese Holstein cows, polymorphisms in the Slc22a7 gene were significantly associated with milk production traits, such as milk yield, fat yield, fat percentage, protein yield, or protein percentage [2]. Genetic variants in Slc22a7 were also associated with anthracycline-induced cardiotoxicity in children, and adding these variants to a prediction model improved its discriminative ability [3].

In conclusion, Slc22a7 is a key transporter with important functions in the transport of various substances and is involved in multiple biological processes and signaling pathways. Studies on mouse models for DKD, as well as research on cows and children, have revealed its potential roles in disease-related conditions, such as DKD and anthracycline-induced cardiotoxicity, and in traits like milk production in cows. These findings highlight the significance of Slc22a7 in different biological and medical contexts.

References:

1. Zhao, Jing, He, Kaiying, Du, Hongxuan, Zhou, Xiaochun, Wang, Jianqin. 2022. Bioinformatics prediction and experimental verification of key biomarkers for diabetic kidney disease based on transcriptome sequencing in mice. In PeerJ, 10, e13932. doi:10.7717/peerj.13932. https://pubmed.ncbi.nlm.nih.gov/36157062/

2. Jia, Ruike, Fu, Yihan, Xu, Lingna, Sun, Dongxiao, Han, Bo. 2021. Associations between polymorphisms of SLC22A7, NGFR, ARNTL and PPP2R2B genes and Milk production traits in Chinese Holstein. In BMC genomic data, 22, 47. doi:10.1186/s12863-021-01002-0. https://pubmed.ncbi.nlm.nih.gov/34732138/

3. Visscher, Henk, Rassekh, S Rod, Sandor, George S, Hayden, Michael R, Ross, Colin J. 2015. Genetic variants in SLC22A17 and SLC22A7 are associated with anthracycline-induced cardiotoxicity in children. In Pharmacogenomics, 16, 1065-76. doi:10.2217/pgs.15.61. https://pubmed.ncbi.nlm.nih.gov/26230641/

4. Sager, Georg, Smaglyukova, Natalia, Fuskevaag, Ole-Martin. 2018. The role of OAT2 (SLC22A7) in the cyclic nucleotide biokinetics of human erythrocytes. In Journal of cellular physiology, 233, 5972-5980. doi:10.1002/jcp.26409. https://pubmed.ncbi.nlm.nih.gov/29244191/

5. Mathialagan, Sumathy, Bi, Yi-An, Costales, Chester, Rodrigues, A David, Varma, Manthena V S. 2020. Nicotinic acid transport into human liver involves organic anion transporter 2 (SLC22A7). In Biochemical pharmacology, 174, 113829. doi:10.1016/j.bcp.2020.113829. https://pubmed.ncbi.nlm.nih.gov/32001236/

6. Sato, Masanobu, Mamada, Hideaki, Anzai, Naohiko, Nakanishi, Takeo, Tamai, Ikumi. . Renal secretion of uric acid by organic anion transporter 2 (OAT2/SLC22A7) in human. In Biological & pharmaceutical bulletin, 33, 498-503. doi:. https://pubmed.ncbi.nlm.nih.gov/20190416/

7. Shen, Hong, Liu, Tongtong, Morse, Bridget L, Marathe, Punit, Lai, Yurong. 2015. Characterization of Organic Anion Transporter 2 (SLC22A7): A Highly Efficient Transporter for Creatinine and Species-Dependent Renal Tubular Expression. In Drug metabolism and disposition: the biological fate of chemicals, 43, 984-93. doi:10.1124/dmd.114.062364. https://pubmed.ncbi.nlm.nih.gov/25904762/

8. Cropp, Cheryl D, Komori, Takafumi, Shima, James E, More, Swati S, Giacomini, Kathleen M. 2008. Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP. In Molecular pharmacology, 73, 1151-8. doi:10.1124/mol.107.043117. https://pubmed.ncbi.nlm.nih.gov/18216183/