Nr1d1-flox Mouse

Nr1d1, also known as REV-ERBα, belongs to the nuclear receptor (NR) family. It is a heme-binding component of the circadian clock that consolidates circadian oscillators. Besides repressing the transcription of multiple clock genes related to circadian rhythms, it has numerous downstream target genes involved in autophagy, immunity, inflammation, metabolism, and aging in various organs [1].

In mouse models, Nr1d1 deficiency in VSMCs inhibited abdominal aortic aneurysm (AAA) formation by restoring ACO2 dysregulation and mitochondrial dysfunction [3]. In MMTV-PyMT transgenic mice, deletion of Nr1d1 led to increased breast tumor growth and lung metastasis, with suppressed type I IFN signaling and T cell-mediated immune responses [2]. In the tumor microenvironment of lung cancer, Nr1d1 deficiency promoted tumor development by activating the NLRP3 inflammasome [4]. In heart-derived Sca-1+CD31-cells, upregulation of Nr1d1 inhibited cell proliferation and promoted apoptosis, while its depletion had the opposite effects [5].

In summary, Nr1d1 is crucial for maintaining normal physiological functions through its regulation of multiple biological processes. Studies using Nr1d1 knockout or conditional knockout mouse models have revealed its significant roles in diseases such as AAA, breast cancer, lung cancer, and in processes related to cell senescence. These findings highlight the potential of Nr1d1 as a therapeutic target for various diseases.