Slc1a1-flox Mouse

Slc1a1, also known as excitatory amino acid carrier 1 (EAAC1), is a sodium-dependent glutamate/cysteine transporter. It plays a central role in regulating neuronal glutathione (GSH) production by transporting glutamate and cystine, which are crucial for GSH synthesis [4]. It is also involved in the regulation of glutamine metabolism and is associated with pathways related to tumor ferroptosis resistance, angiogenesis, and lymphoma progression [1,2,3].

In natural killer T-cell lymphoma (NKTCL), SLC1A1 overexpression in vitro and in zebrafish xenograft models increased cellular glutamine uptake, enhanced GSH metabolic flux, and induced glutamine addiction, accelerating cell proliferation and tumor growth. Asparaginase treatment counteracted SLC1A1-mediated glutamine addiction [3]. In IDH1-mutant solid tumors, SLC1A1 deficiency in mice abolished mIDH1-promoted tumor angiogenesis and the therapeutic benefit of mIDH1 inhibitor, as SLC1A1 facilitates the influx of R-2-hydroxyglutarate (R-2-HG) from the tumor microenvironment into endothelial cells [2]. In solid tumors, silencing HIF-1α, which enhances SLC1A1 transcription, sensitizes mouse solid tumors to ferroptosis inducers, indicating SLC1A1's role in hypoxia-induced ferroptosis resistance [1].

In conclusion, Slc1a1 is essential for processes such as GSH synthesis, glutamine metabolism, and is involved in multiple disease-related pathways including tumor angiogenesis, ferroptosis resistance, and NKTCL progression. Studies using gene knockout or knockdown models in mice and other organisms have been instrumental in revealing its role in these disease areas, providing potential therapeutic targets for treating related diseases.