Slc31a1-flox Mouse

Slc31a1, also known as CTR1, encodes a protein that functions as a homotrimer for the uptake of dietary copper. It is an important copper transporter in the cell membrane, influencing copper absorption and thus playing a crucial role in maintaining copper homeostasis, which is essential for the activity of numerous copper-containing enzymes involved in various biological processes [4,5,7].

In a study on cardiac fibrosis, fibroblast-specific SLC31A1 deficiency enhanced mitochondrial copper depletion, augmented glycolysis, promoted fibroblast proliferation, and triggered cardiac fibrosis, suggesting that SLC31A1 is crucial in preventing mitochondrial copper depletion-related cardiac fibrosis [3].

In diabetic conditions, excessive advanced glycosylation end products (AGEs) and copper up-regulated the ATF3/SPI1/SLC31A1 signaling, disturbing copper homeostasis and promoting cuproptosis in the myocardium, indicating its role in diabetic myocardial injury [1].

High SLC31A1 expression in breast cancer was related to deregulated immune response, metabolic pathways, and predicted poor prognosis, suggesting its significance in breast cancer prognosis and immune-related processes [2].

In pan-cancer analysis, SLC31A1 expression was significantly different between tumors and normal tissues in nine cancer types, and was linked to immune cell infiltration, immune checkpoint genes, and immunotherapy markers, highlighting its potential in cancer immunotherapy [4].

In diabetic retinopathy, SLC31A1 was up-regulated, and it may be involved in the regulation of cuproptosis through the STAT1-SLC31A1 axis [6].

In cisplatin-induced acute kidney injury, SLC31A1 was up-regulated by ELF3, and its activation triggered cuproptosis through mitochondrial dysfunction, making it a potential therapeutic target to mitigate this injury [8].

In conclusion, Slc31a1 is essential for copper homeostasis. Its dysregulation is associated with various diseases such as cardiac fibrosis, diabetic complications, and cancers. Studies using gene-knockout or conditional-knockout mouse models, as well as other in-vivo studies, have revealed its critical roles in these disease-related biological processes, providing potential therapeutic targets for these conditions.