Nr3c1-flox Mouse

Nr3c1, also known as the glucocorticoid receptor gene, encodes the glucocorticoid receptor, which functions as both a transcription factor and an RNA-binding protein. It is a crucial component of the stress-response system and is involved in the hypothalamus-pituitary-adrenal (HPA) axis. Glucocorticoids bind to the receptor, influencing the expression of numerous target genes, thereby regulating a wide range of biological processes such as metabolism, inflammation, and immune response [3,4,5].

Knockdown of Nr3C1 in clear cell renal cell carcinoma (ccRCC) cells reduces their proliferation and migration capacity. This occurs through the activation of endoplasmic reticulum stress-mitophagy via the ATF6-PINK1/BNIP3 pathway [2]. In pancreatic β-cells, activation of Nr3C1 promotes autophagy overload under glucolipotoxic conditions. Specifically, Nr3C1-enhancement upregulates the RNA demethylase FTO, leading to hyperactive autophagy and defective insulin output, which eventually promotes diabetes [1].

In conclusion, Nr3c1 is essential in regulating stress responses, metabolism, and cell function. Studies using loss-of-function models have revealed its significant roles in diseases such as diabetes and ccRCC. Understanding Nr3c1's functions through these models provides potential therapeutic targets for treating related diseases.