Slc5a12-KO Mouse

Slc5a12, also known as SMCT2, is a sodium-coupled low-affinity transporter for monocarboxylates. It is involved in the transport of substances like lactate, nicotinate, propionate and butyrate, and plays a role in processes such as the reabsorption of lactate in the kidney, absorption of diet-derived short-chain monocarboxylates in the intestinal tract, and in T cell-related metabolic and migration processes [2,3,4].

In c/ebpdelta -/- mice, where the renal expression of both Slc5a8 and Slc5a12 is almost completely ablated, there is a marked increase in urinary excretion of lactate and a decrease in blood lactate levels, providing evidence for the role of Slc5a12 in renal lactate absorption [5]. In a murine model of arthritis, antibody-mediated blockade of Slc5a12 ameliorates disease severity, suggesting its role in chronic inflammatory disorders [1].

In conclusion, Slc5a12 is crucial for monocarboxylate transport in the body, especially in the kidney and intestine. Gene-knockout models like c/ebpdelta -/- mice have revealed its role in renal lactate handling. Its function in T cell-mediated inflammation, as shown by the murine arthritis model, indicates its potential as a therapeutic target for chronic inflammatory diseases.

References:

1. Pucino, Valentina, Certo, Michelangelo, Bulusu, Vinay, Pitzalis, Costantino, Mauro, Claudio. 2019. Lactate Buildup at the Site of Chronic Inflammation Promotes Disease by Inducing CD4+ T Cell Metabolic Rewiring. In Cell metabolism, 30, 1055-1074.e8. doi:10.1016/j.cmet.2019.10.004. https://pubmed.ncbi.nlm.nih.gov/31708446/

2. Srinivas, Sonne R, Gopal, Elangovan, Zhuang, Lina, Ganapathy, Vadivel, Prasad, Puttur D. . Cloning and functional identification of slc5a12 as a sodium-coupled low-affinity transporter for monocarboxylates (SMCT2). In The Biochemical journal, 392, 655-64. doi:. https://pubmed.ncbi.nlm.nih.gov/16104846/

3. Plata, Consuelo, Sussman, Caroline R, Sindic, Aleksandra, Chang, Min-Hwang, Romero, Michael F. 2007. Zebrafish Slc5a12 encodes an electroneutral sodium monocarboxylate transporter (SMCTn). A comparison with the electrogenic SMCT (SMCTe/Slc5a8). In The Journal of biological chemistry, 282, 11996-2009. doi:. https://pubmed.ncbi.nlm.nih.gov/17255103/

4. Gopal, E, Umapathy, N S, Martin, P M, Ganapathy, V, Prasad, P D. 2007. Cloning and functional characterization of human SMCT2 (SLC5A12) and expression pattern of the transporter in kidney. In Biochimica et biophysica acta, 1768, 2690-7. doi:. https://pubmed.ncbi.nlm.nih.gov/17692818/

5. Thangaraju, Muthusamy, Ananth, Sudha, Martin, Pamela M, Prasad, Puttur D, Ganapathy, Vadivel. 2006. c/ebpdelta Null mouse as a model for the double knock-out of slc5a8 and slc5a12 in kidney. In The Journal of biological chemistry, 281, 26769-73. doi:. https://pubmed.ncbi.nlm.nih.gov/16873376/