Trib3-KO Mouse

TRIB3, also known as tribbles pseudokinase 3, is a multifunctional protein induced by endoplasmic reticulum stress (ERS). It has a "pseudokinase" function that can inactivate multiple transcription factors and signaling proteins. TRIB3 is involved in various pathways such as PI3K/AKT/mTOR and autophagy, playing a crucial role at the junction of health, metabolic dysfunction, and cancer [5]. Genetic models like KO/CKO mouse models are valuable for studying its functions.

In a diet-induced NAFLD mouse model, disrupting the TRIB3-HNF4α interaction using a cell-penetrating peptide restored HNF4α levels and ameliorated NAFLD progression, indicating that the TRIB3-TRIM8 E3 complex-mediated HNF4α polyubiquitination is involved in NAFLD pathogenesis [1]. In CRC mouse models, genetic ablation of Trib3 increased T cell recruitment and sensitized CRCs to immune checkpoint blockade therapy, as TRIB3 inhibits CD8+ T cell infiltration by repressing the STAT1-CXCL10 axis [2]. In mouse models of hepatic fibrosis induced by bile duct ligation or thioacetamide injection, silencing Trib3 protected against fibrosis, accompanied by restored autophagy activity [3]. In ApcMin/J mice, knockdown of Trib3 decreased colon neoplasia, while overexpression of Trib3 promoted tumorigenesis, suggesting its role in CRC development [4].

In conclusion, TRIB3 is involved in multiple biological processes and diseases. Studies using KO/CKO mouse models have revealed its roles in non-alcoholic fatty liver disease, colorectal cancer, hepatic fibrosis, etc. These findings help to understand the mechanisms of these diseases and provide potential therapeutic targets related to TRIB3.