Per1-flox Mouse

Per1, also known as Period circadian regulator 1, is a core component of the circadian clock [4,5,6,7,8,9,10]. It functions with other clock components to generate a feedback loop involving the transcriptional repression of gene expression, producing a circadian rhythm with an approximately 24-hour cycle [9]. PER1 is involved in regulating various biological processes, such as metabolism, immune response, and cell cycle regulation, and is associated with multiple pathways [1,2,3,5,6,7,8,10].

In trastuzumab-resistant HER2-positive gastric cancer cells, PER1, along with PPARγ, regulates the circadian oscillation of HK2-dependent glycolysis, and silencing PER1 disrupts this rhythm and reverses trastuzumab resistance [1]. In pancreatic cancer, the m6A demethylase ALKBH5 post-transcriptionally activates PER1, which in turn re-activates the ATM-CHK2-P53/CDC25C signalling to inhibit cell growth [2]. In ocular melanoma, histone lactylation promotes YTHDF2 expression, and YTHDF2 recognizes m6A-modified PER1 mRNA and promotes its degradation, accelerating tumorigenesis [3]. In mice, Per1 deficiency deregulates daily oxygen consumption rhythm, mitochondrial dynamics, and cellular GPx-related ROS fluctuations [6]. In rat mandibular condylar chondrocytes, PER1 can regulate the expression of MMP13 through the NF-κB pathway in IL-1β-induced cells [7]. In hindlimb ischemia (HLI) mouse models, PER1 overexpression promotes functional recovery by reducing M1 macrophage polarization and promoting M2 macrophage polarization [8]. In rats, WNK3 can phosphorylate PER1 to promote its degradation and is associated with circadian oscillations [9]. In ovarian cancer, PER1 expression is lower in tumor tissues, and low PER1 expression is related to a reduced overall survival rate [10].

In conclusion, Per1 is crucial for maintaining the circadian rhythm and is involved in various biological processes and diseases. Studies using gene-knockout or conditional-knockout mouse models and other loss-of-function experiments have revealed its significant role in cancer, metabolic diseases, and inflammatory conditions, providing valuable insights into potential therapeutic targets and disease mechanisms [1,2,3,5,6,7,8,9,10].