Trib1-KO Mouse

TRIB1, a member of the Tribbles homolog (TRIB) protein family, is a pseudokinase. It plays diverse roles in biological conditions, regulating intracellular signaling networks. TRIB1 directly interacts with transcription factors like FOXP3 and C/EBPα, signaling molecules such as MEK1 and MALT1, and acts on key pathways including MAPK and NF-κB, being at the center of major cell signaling pathways with cell-specific roles [1].

In liver regeneration, Trib1 expression was transiently down-regulated. Knockdown of Trib1 enhanced while over-expression suppressed liver regeneration after partial hepatectomy in mice. Trib1 influenced cellular redox status by attenuating Nrf2 activity, suggesting a link between intracellular redox homeostasis and cell proliferation in liver regeneration [2]. In atherosclerotic-susceptible Ldlr-/-mice, Trib1 deficiency led to larger and more advanced atherosclerotic lesions, elevated plasma total cholesterol and triglyceride levels, and signs of hepatic inflammation and injury, indicating Trib1 deficiency promotes atherosclerotic lesion formation through modulating lipid metabolism and inflammation [3].

In conclusion, TRIB1 is crucial in multiple biological processes. The gene knockout mouse models, like in liver regeneration and atherosclerosis studies, have revealed its important roles in regulating cell proliferation, redox homeostasis, lipid metabolism, and inflammation, providing insights into related disease mechanisms.

References:

1. Danger, Richard, Feseha, Yodit, Brouard, Sophie. 2022. The Pseudokinase TRIB1 in Immune Cells and Associated Disorders. In Cancers, 14, . doi:10.3390/cancers14041011. https://pubmed.ncbi.nlm.nih.gov/35205759/

2. Sun, Xinyue, Wang, Shuai, Miao, Xiulian, Xu, Yong, Li, Zilong. 2023. TRIB1 regulates liver regeneration by antagonizing the NRF2-mediated antioxidant response. In Cell death & disease, 14, 372. doi:10.1038/s41419-023-05896-9. https://pubmed.ncbi.nlm.nih.gov/37355685/

3. Arndt, Lilli, Hernandez-Resendiz, Ileana, Moos, Doreen, Stadler, Sonja C, Burkhardt, Ralph. 2023. Trib1 Deficiency Promotes Hyperlipidemia, Inflammation, and Atherosclerosis in LDL Receptor Knockout Mice. In Arteriosclerosis, thrombosis, and vascular biology, 43, 979-994. doi:10.1161/ATVBAHA.122.318137. https://pubmed.ncbi.nlm.nih.gov/37078290/