Bmal1-flox Mouse

Bmal1, also known as Brain and muscle arnt-like protein 1, is a crucial transcription factor and a core component of the circadian oscillation. It forms a heterodimer with Clock, binding to the E-box element in the promoters of genes like Per and Cry, regulating the rhythmic expression of circadian clock-controlled genes. Bmal1 is involved in maintaining immune homeostasis, and is associated with pathways related to metabolism, immunity, and reproduction, playing an overall vital role in various biological processes [2].

In disease-related studies, Bmal1 down-regulation in cardiomyocyte-specific knockout (CKB) and type 2 diabetes (T2D) mice hearts accelerates cardiac hypertrophy and diastolic dysfunction, while overexpression alleviates these pathological changes in diabetic cardiomyopathy (DCM), suggesting its role in DCM development through Bcl2/IP3R-mediated mitochondrial Ca2+ overload [1]. In Bmal1 -/- mutant mice (a model with non-functional circadian clock), colitis is more severe, with constant disease activity, impaired recovery, and loss of daily rhythms in inflammation and epithelial proliferation, indicating Bmal1's importance in regulating the daily timing of colitis [3]. In AML, knocking down BMAL1 inhibits cell growth by blocking the cell cycle and promotes ferroptosis, enhancing the efficacy of certain cancer therapeutic drugs, as BMAL1 up-regulation is observed in AML patients with poor prognosis [4].

In conclusion, Bmal1 is essential for maintaining normal physiological functions related to circadian rhythms, immune homeostasis, and metabolism. The use of gene knockout (KO) and conditional knockout (CKO) mouse models has revealed its significant roles in diseases such as DCM, colitis, and AML, providing potential therapeutic targets for these diseases.