Trim24-KO Mouse

TRIM24, also known as TRIpartite motif-containing protein 24, is an E3 ligase with diverse functions. It is involved in multiple biological pathways, such as those related to macrophage polarization, DNA damage response, and insulin signaling, and is of great biological importance in processes like tumorigenesis, immune response, and metabolic regulation [1,2,3,4]. Genetic models, especially knockout (KO) mouse models, are valuable for studying its functions.

In macrophage polarization, loss of Trim24 inhibits Stat6 acetylation and promotes M2 polarization, potentially compromising antitumor immune responses, while Stat6 suppresses TRIM24 expression in M2 macrophages, contributing to an immunosuppressive tumor niche [1]. In nasopharyngeal carcinoma, depletion of TRIM24 inhibits M1 macrophage polarization, facilitating NPC cell growth and migration [2]. Regarding DNA double-strand breaks, in the absence of TRIM24, MRN-mediated DSBs repair is diminished, and depletion of TRIM24 sensitizes human hepatocellular carcinoma cells to apoptosis and retards tumor growth in a xenograft model [3]. In allergic rhinitis, TRIM24-conditional knockout mice with TRIM24 deficiency in CD4+ T cells have more severe AR symptoms, and TRIM24-knockout CD4+ T cells have enhanced Th2 polarization [5].

In conclusion, TRIM24 plays essential roles in macrophage polarization, DNA damage repair, and allergic response through its functions in acetylation regulation, recruitment of protein complexes, and interaction with signaling molecules. The use of KO/CKO mouse models has significantly advanced our understanding of its role in tumor-related diseases and allergic rhinitis, providing potential therapeutic targets for these conditions.

References:

1. Yu, Tao, Gan, Shucheng, Zhu, Qingchen, Qin, Jun, Xiao, Yichuan. 2019. Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24. In Nature communications, 10, 4353. doi:10.1038/s41467-019-12384-2. https://pubmed.ncbi.nlm.nih.gov/31554795/

2. Liu, Huai, Tang, Ling, Gong, Sha, Wang, Hui, Chen, Pan. 2023. USP7 inhibits the progression of nasopharyngeal carcinoma via promoting SPLUNC1-mediated M1 macrophage polarization through TRIM24. In Cell death & disease, 14, 852. doi:10.1038/s41419-023-06368-w. https://pubmed.ncbi.nlm.nih.gov/38129408/

3. Wang, Ya, Yao, Yuanbing, Wei, Qunhui, Wan, Fengyi, Fu, Kai. 2022. TRIM24 is critical for the cellular response to DNA double-strand breaks through regulating the recruitment of MRN complex. In Oncogene, 42, 586-600. doi:10.1038/s41388-022-02580-8. https://pubmed.ncbi.nlm.nih.gov/36550358/

4. Wei, Wen, Chen, Qiaoli, Liu, Minjun, Wang, Hong-Yu, Chen, Shuai. 2022. TRIM24 is an insulin-responsive regulator of P-bodies. In Nature communications, 13, 3972. doi:10.1038/s41467-022-31735-0. https://pubmed.ncbi.nlm.nih.gov/35803934/

5. Yue, Liyan, Jia, Qiaojing, Dong, Jinhui, Ren, Xiumin, Xu, Ou. . TRIM24-Mediated Acetylation of STAT6 Suppresses Th2-Induced Allergic Rhinitis. In Allergy, asthma & immunology research, 15, 603-613. doi:10.4168/aair.2023.15.5.603. https://pubmed.ncbi.nlm.nih.gov/37827979/