Slc7a13-KO Mouse

Slc7a13, also known as AGT1, is a membrane protein that functions as a cystine transporter. It is localized in the apical membrane of the S3 segment of renal proximal tubules, where it forms a heterodimer with rBAT/SLC3A1 and transports cystine, aspartate, and glutamate [4].

In the context of cystinuria, a disease caused by defective renal reabsorption of cystine and dibasic amino acids, screening of 17 cystinuria patients negative for SLC3A1 and SLC7A9 mutations found no evidence that SLC7A13 point mutations contribute to the etiology of cystinuria [2]. However, it is still considered a promising candidate gene for cystinuria, needing further research to determine its involvement in human cystinuria [3]. In a study on urolithiasis, Slc7a13 was among the functional solute carriers used to identify distinct injured-proximal tubular cell types in calculi rats, providing insights into kidney injury in urolithiasis [1].

In conclusion, Slc7a13 plays a significant role as a cystine transporter in the renal proximal tubules. Although current evidence from some studies does not support its role in the etiology of cystinuria in certain patient cohorts, it remains a potential candidate gene for further exploration in cystinuria research. The identification of its role in urolithiasis-related kidney injury also expands our understanding of its function in kidney-related diseases.

References:

1. Wang, Zhu, Deng, Qiong, Gu, Yanli, Wang, Xisheng, Liang, Hui. 2023. Integrated single-nucleus sequencing and spatial architecture analysis identified distinct injured-proximal tubular types in calculi rats. In Cell & bioscience, 13, 92. doi:10.1186/s13578-023-01041-3. https://pubmed.ncbi.nlm.nih.gov/37208718/

2. Olschok, Kathrin, Vester, Udo, Lahme, Sven, Kurth, Ingo, Eggermann, Thomas. 2018. No evidence for point mutations in the novel renal cystine transporter AGT1/SLC7A13 contributing to the etiology of cystinuria. In BMC nephrology, 19, 278. doi:10.1186/s12882-018-1080-5. https://pubmed.ncbi.nlm.nih.gov/30342472/

3. Abad Baucells, Clàudia, Schönauer, Ria, Halbritter, Jan. 2023. The genetics of cystinuria - an update and critical reevaluation. In Current opinion in nephrology and hypertension, 33, 231-237. doi:10.1097/MNH.0000000000000949. https://pubmed.ncbi.nlm.nih.gov/38240263/

4. Nagamori, Shushi, Wiriyasermkul, Pattama, Guarch, Meritxell Espino, Palacín, Manuel, Kanai, Yoshikatsu. 2016. Novel cystine transporter in renal proximal tubule identified as a missing partner of cystinuria-related plasma membrane protein rBAT/SLC3A1. In Proceedings of the National Academy of Sciences of the United States of America, 113, 775-80. doi:10.1073/pnas.1519959113. https://pubmed.ncbi.nlm.nih.gov/26739563/