Map3k7-KO Mouse

Map3k7, also known as TAK1 (Transforming growth factor-β -activated kinase 1), is a member of the MAPK kinase kinase (MAPKKK) family. It has a wide-ranging impact on physiological and pathological processes, playing essential roles in the activation of NF-κB and MAPKs pathways. It is activated by stimuli like TNFα, IL-1β, and toll-like receptor ligands. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions [3].

In prostate cancer, Map3k7 knockout increased AR protein levels and activity in the mouse prostate, revealing a tumor-suppressive role of the MAP3K7-IKKβ axis in degrading AR protein [1]. In hypertensive nephropathy, TRIM31 -/- mice showed aggravated hypertension-induced renal dysfunction as TRIM31 promotes proteasomal degradation of MAP3K7, negatively regulating TGF-β1-mediated signaling pathways [2]. In mouse embryonic stem cells, Map3k7-overexpressing embryoid bodies had increased AVE markers, and inhibition of Map3k7 decreased endoderm differentiation, suggesting it governs cardiogenic endoderm formation [4].

In conclusion, Map3k7 is a crucial regulator in multiple biological processes and disease conditions. Mouse models, especially those with Map3k7 knockout or overexpression, have provided insights into its role in prostate cancer, hypertensive nephropathy, and cardiogenic endoderm differentiation, highlighting its potential as a therapeutic target and biomarker in these disease areas.

References:

1. Huang, Zhenlin, Tang, Bo, Yang, Yinhui, Jia, Zhankui, Huang, Haojie. 2021. MAP3K7-IKK Inflammatory Signaling Modulates AR Protein Degradation and Prostate Cancer Progression. In Cancer research, 81, 4471-4484. doi:10.1158/0008-5472.CAN-20-4194. https://pubmed.ncbi.nlm.nih.gov/34158377/

2. Zhang, Jie, Cao, Lei, Wang, Xiaohong, Zhang, Meng, Zhang, Yun. 2021. The E3 ubiquitin ligase TRIM31 plays a critical role in hypertensive nephropathy by promoting proteasomal degradation of MAP3K7 in the TGF-β1 signaling pathway. In Cell death and differentiation, 29, 556-567. doi:10.1038/s41418-021-00874-0. https://pubmed.ncbi.nlm.nih.gov/34584221/

3. Xu, Yan-Ran, Lei, Cao-Qi. 2021. TAK1-TABs Complex: A Central Signalosome in Inflammatory Responses. In Frontiers in immunology, 11, 608976. doi:10.3389/fimmu.2020.608976. https://pubmed.ncbi.nlm.nih.gov/33469458/

4. Hunter, Andrew, Dai, Yunkai, Brown, Kemar J, Muise-Helmericks, Robin C, Foley, Ann C. 2019. TAK1/Map3k7 enhances differentiation of cardiogenic endoderm from mouse embryonic stem cells. In Journal of molecular and cellular cardiology, 137, 132-142. doi:10.1016/j.yjmcc.2019.10.002. https://pubmed.ncbi.nlm.nih.gov/31668971/