Nr3c1-KO 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 key component of the stress-response system and is involved in multiple biological processes by regulating the hypothalamus-pituitary-adrenal (HPA) axis. Genetic models, such as KO/CKO mouse models, have been crucial in studying its functions.

Knockdown of Nr3c1 in clear cell renal cell carcinoma (ccRCC) cells inhibits their proliferation and migration through activating endoplasmic reticulum stress-mitophagy via the ATF6-PINK1/BNIP3 pathway [2]. In pancreatic β-cells, activation of Nr3c1 promotes autophagy overload under glucolipotoxic conditions. The NR3C1-FTO-m6A modifications-Atg genes axis is a key mediator of balanced autophagic flux, and inhibition of FTO can prevent excessive autophagy activation, which may offer a new therapeutic target for diabetes [1].

In summary, Nr3c1 is essential in regulating stress-related biological processes and is implicated in diseases like diabetes and ccRCC. Studies using KO/CKO mouse models have revealed its role in these disease conditions, highlighting its potential as a therapeutic target.