Slc13a3-flox Mouse

Slc13a3, encoding the plasma membrane Na+/dicarboxylate cotransporter 3 (NaDC3), imports 4-6 carbon dicarboxylates and N-acetylaspartate (NAA) into cells. It is mainly expressed in the kidney, astrocytes, and choroid plexus, and is involved in various biological processes. In the immune-related context, it participates in the crosstalk between tumors and macrophages and is associated with immunomodulatory and ferroptosis-related pathways [1,3,4]. In liver cancer, it is an effector downstream of activated β-catenin [2].

In in vivo studies, genetic ablation of Slc13a3 in tumors sensitizes tumors to ferroptosis, curbs tumor progression, and enhances immune checkpoint blockade (ICB) effectiveness, indicating its role in tumor immunity evasion [1]. In liver-specific Slc13a3 knockout mouse models, hepatic antibacterial innate immunity is impaired, suggesting its importance in this immune process [3]. In astroglial conditional Slc13a3 knockout mice (relevant to Canavan leukodystrophy), brain N-acetyl-l-aspartate (NAA) elevation is reversed and motor function is improved [5].

In conclusion, Slc13a3 is crucial in multiple biological functions, especially in tumor immunity, hepatic antibacterial innate immunity, and Canavan leukodystrophy-related processes. The gene knockout and conditional knockout mouse models have significantly contributed to revealing its roles in these disease-related areas, providing potential therapeutic targets for cancer, antibacterial treatment, and Canavan disease.