Trim60-KO Mouse

Trim60, also known as RNF33, is a gene with diverse functions. It encodes a tripartite motif (TRIM)/RBCC protein. In the innate immune response, it is involved in regulating the TAK1 signalosome, and thus has an impact on the MAPK/NF-κB activation pathways. It also seems to play a role in spermatogenesis, potentially through its interaction with kinesin motor proteins in the testis [2,3].

In terms of core findings, TRIM60 -deficient macrophages showed enhanced MAPK and NF-κB activation, along with elevated levels of proinflammatory cytokines. TRIM60 was found to SUMOylate TAB2 rather than ubiquitinate it, which impaired the formation of the TRAF6/TAB2/TAK1 complex and downstream pathways. In vivo, TRIM60 -deficient mice had an elevated immune response to LPS-induced septic shock and L. monocytogenes infection, revealing its role in the innate immune response [1].

In conclusion, Trim60 is essential for regulating the innate immune response, likely through its SUMOylation of TAB2 and modulation of the TAK1 signalosome. The gene knockout mouse models have been instrumental in revealing its role in controlling antibacterial immune responses, providing valuable insights into the underlying molecular mechanisms of the innate immune system [1].

References:

1. Gu, Zhiwen, Chen, Xueying, Yang, Wenyong, Zhang, Huiyuan, Hu, Hongbo. 2020. The SUMOylation of TAB2 mediated by TRIM60 inhibits MAPK/NF-κB activation and the innate immune response. In Cellular & molecular immunology, 18, 1981-1994. doi:10.1038/s41423-020-00564-w. https://pubmed.ncbi.nlm.nih.gov/33184450/

2. Huang, Chiu-Jung, Huang, Chih-Cheng, Chang, Chih-Chun. 2011. Association of the testis-specific TRIM/RBCC protein RNF33/TRIM60 with the cytoplasmic motor proteins KIF3A and KIF3B. In Molecular and cellular biochemistry, 360, 121-31. doi:10.1007/s11010-011-1050-8. https://pubmed.ncbi.nlm.nih.gov/21909995/

3. Choo, Kong-Bung, Hsu, Min-Chuan, Tsai, Yao-Hui, Lin, Wan-Yi, Huang, Chiu-Jung. 2011. Nuclear factor kappa B and tumor necrosis factor-alpha modulation of transcription of the mouse testis- and pre-implantation development-specific Rnf33/Trim60 gene. In The FEBS journal, 278, 837-50. doi:10.1111/j.1742-4658.2010.08002.x. https://pubmed.ncbi.nlm.nih.gov/21205214/