Slc1a5-flox Mouse

Slc1a5, also known as alanine-serine-cysteine transporter 2 (ASCT2), is a key neutral amino-acid exchanger and well-studied glutamine transporter. Glutamine, transported by Slc1a5, is essential for regulating energy production, redox homeostasis, and signaling in cells. It is involved in multiple pathways such as mTORC1 activation through amino-acid sensing, and is crucial for cell metabolism, growth, and proliferation [1].

In Slc1a5-deficient mice, the rate of glutamine uptake in bone marrow cells was reduced, and the formation of multinucleated osteoclasts was severely impaired. RANKL-induced expression of ERK, NFκB, p70S6K, and NFATc1 was also suppressed in Slc1a5 -/- osteoclasts, indicating its important role in osteoclast formation [5]. In cancer cells, knockdown of Slc1a5 in melanoma cells increased their sensitivity to erastin-and RSL3-induced ferroptosis [2]. In gastric cancer cells, quercetin inhibited Slc1a5 expression, leading to ferroptosis [3]. In leukemia stem cells, genetic inhibition of Slc1a5 phenocopied the impairment of oxidative phosphorylation observed with STAT3 inhibition, reducing intracellular levels of glutamine, glutathione, and TCA cycle metabolites [4].

In conclusion, Slc1a5 plays essential roles in cell metabolism, especially in glutamine transport. Its deficiency in mouse models has revealed its significance in osteoclastogenesis and in the context of various cancers, including melanoma, gastric cancer, and leukemia. Understanding Slc1a5 function through these models provides insights into disease mechanisms and potential therapeutic targets.