Per2-KO Mouse

Per2, short for Period2, is a core component of the circadian rhythm, playing a vital role in regulating the circadian rhythm of the biological clock [3]. It is involved in various pathways and biological processes, regulating multiple physiological systems like metabolism, sleep, and immune function [4]. Genetic models, such as the PER2::LUC knockin mouse, have been crucial for studying its spatiotemporal patterns in the suprachiasmatic nuclei [5].

In disease-related research, in oral squamous cell carcinoma (OSCC), PER2 expression is reduced. Overexpression of PER2 inhibits PD-L1 expression by suppressing the IKK/NF-κB pathway, enhancing T-cell-mediated OSCC cell killing [1]. In pituitary adenomas, PER2 is prominently upregulated. Jetlagged mice with PER2 upregulation have accelerated growth of GH3 xenograft tumors, while loss of Per2 protects mice against developing estrogen-induced pituitary adenoma, suggesting PER2 promotes pituitary tumorigenesis by regulating cell cycle genes [2]. In ulcerative colitis, PER2 is decreased in inflamed mucosa and peripheral blood CD4+ T cells of patients. Overexpression of PER2 in UC CD4+ T cells inhibits IFN-γ production by down-regulating ADAM12 [6].

In conclusion, Per2 is essential for regulating the circadian rhythm and is involved in multiple biological processes. Through gene knockout and other model-based research, it has been shown to play significant roles in diseases such as OSCC, pituitary adenomas, and ulcerative colitis, providing potential therapeutic targets for these conditions.

References:

1. Zhang, Zhiwei, Sun, Deping, Tang, Hong, Yin, Shilin, Yang, Kai. . PER2 binding to HSP90 enhances immune response against oral squamous cell carcinoma by inhibiting IKK/NF-κB pathway and PD-L1 expression. In Journal for immunotherapy of cancer, 11, . doi:10.1136/jitc-2023-007627. https://pubmed.ncbi.nlm.nih.gov/37914384/

2. Guo, Lianxia, Cen, Haobin, Weng, Jiaxian, Chen, Zhiyong, Wu, Baojian. 2023. PER2 integrates circadian disruption and pituitary tumorigenesis. In Theranostics, 13, 2657-2672. doi:10.7150/thno.82995. https://pubmed.ncbi.nlm.nih.gov/37215573/

3. Jiang, Huihui, Yang, Xin, Mi, Miaomiao, Xin, Yu, Sun, Chengming. 2021. PER2: a potential molecular marker for hematological malignancies. In Molecular biology reports, 48, 7587-7595. doi:10.1007/s11033-021-06751-w. https://pubmed.ncbi.nlm.nih.gov/34642831/

4. Pavithra, S, Aich, Adrija, Chanda, Adrita, Gawade, Pranotee, Das, Raunak Kumar. 2023. PER2 gene and its association with sleep-related disorders: A review. In Physiology & behavior, 273, 114411. doi:10.1016/j.physbeh.2023.114411. https://pubmed.ncbi.nlm.nih.gov/37981094/

5. Leise, Tanya L. . Computational Analysis of PER2::LUC Imaging Data. In Methods in molecular biology (Clifton, N.J.), 2130, 295-302. doi:10.1007/978-1-0716-0381-9_22. https://pubmed.ncbi.nlm.nih.gov/33284453/

6. Ye, Yulan, Liu, Changqin, Wu, Ruijin, Liu, Zhanju, Chen, Liang. 2024. Circadian clock component PER2 negatively regulates CD4+ T cell IFN-γ production in ulcerative colitis. In Mucosal immunology, 17, 1161-1173. doi:10.1016/j.mucimm.2024.07.010. https://pubmed.ncbi.nlm.nih.gov/39097147/