TRIM67, a member of the tripartite motif (TRIM) protein family, is an E3 ubiquitin ligase. It plays essential roles in neuronal development and is involved in multiple biological processes such as regulation of inflammatory pathways, including the NF-κB signaling pathway, and is also associated with cell-cycle arrest, apoptosis, and DNA repair [1,2]. Genetic models like knockout mouse models are valuable for studying its functions.

In Trim67 knockout ApcMin/+ mice, there was an increased incidence, multiplicity, and burden of colorectal tumors, indicating its role as a tumor suppressor in colorectal cancer, mediated by activation of the p53 signaling pathway [2]. In obese mice with TRIM67 deficiency, there was exacerbated hypothalamic inflammation, apoptosis, and fat accumulation, suggesting its importance in body-energy homeostasis [3]. In the olfactory bulb of Trim67 knockout mice, there was excessive proliferation of mitral cells and defects in synaptic development, leading to reduced olfactory function [4].

In conclusion, TRIM67 has diverse biological functions, mainly in neuronal development, regulation of inflammation, and tumorigenesis. The use of gene knockout mouse models has been crucial in revealing its role in colorectal cancer, obesity-related metabolic disorders, and olfactory function, providing insights into the mechanisms of these diseases and potential therapeutic targets.

References:

1. Fan, Wenchun, Liu, Xueyan, Zhang, Jinyan, Chen, Huanchun, Qian, Ping. 2022. TRIM67 Suppresses TNFalpha-Triggered NF-kB Activation by Competitively Binding Beta-TrCP to IkBa. In Frontiers in immunology, 13, 793147. doi:10.3389/fimmu.2022.793147. https://pubmed.ncbi.nlm.nih.gov/35273593/

2. Wang, Shiyan, Zhang, Yanquan, Huang, Junzhe, Zhao, Zengren, Yu, Jun. 2019. TRIM67 Activates p53 to Suppress Colorectal Cancer Initiation and Progression. In Cancer research, 79, 4086-4098. doi:10.1158/0008-5472.CAN-18-3614. https://pubmed.ncbi.nlm.nih.gov/31239268/

3. Jia, Lanlan, Chen, Zhengli, Pan, Ting, Huang, Chao, Luo, Qihui. 2022. TRIM67 Deficiency Exacerbates Hypothalamic Inflammation and Fat Accumulation in Obese Mice. In International journal of molecular sciences, 23, . doi:10.3390/ijms23169438. https://pubmed.ncbi.nlm.nih.gov/36012700/

4. Cai, Chunyu, Luo, Qihui, Jia, Lanlan, Huang, Chao, Chen, Zhengli. 2023. TRIM67 Implicates in Regulating the Homeostasis and Synaptic Development of Mitral Cells in the Olfactory Bulb. In International journal of molecular sciences, 24, . doi:10.3390/ijms241713439. https://pubmed.ncbi.nlm.nih.gov/37686246/