Dusp2-KO Mouse

Dusp2, a member of the mitogen-activated protein kinase phosphatase family, is crucial for regulating multiple cellular processes. It participates in modulating various signaling pathways, such as the AKT1, MEK/ERK, and P38 MAPK pathways, and is involved in immune responses, inflammation, and cancer progression [1,2]. Genetic models, like gene knockout (KO) mouse models, have been valuable in exploring its functions.

In pancreatic cancer, DUSP2 promotes apoptosis by competing with AKT1 to bind CSNK2A1, inhibiting AKT1 phosphorylation, while activation of AKT1 leads to DUSP2 degradation via the AKT1/TRIM21 loop [1]. In bladder cancer, its down-regulation is associated with poor prognosis, and overexpression inhibits cancer cell proliferation, metastasis, and affects the immune microenvironment by regulating MEK/ERK and P38 MAPK through the PTPN7 pathway [2,5]. In acute kidney injury, RTEC-specific deletion of DUSP2 in mice promotes tubular epithelial cell pyroptosis and interstitial inflammation, while DUSP2 overexpression ameliorates AKI by deactivating STAT1 to restrict GSDMD-mediated pyroptosis [3]. In zebrafish, knocking out Dusp2 promotes Mauthner cell axonal regeneration at the early stage, possibly through enhancing JNK phosphorylation [4].

In conclusion, Dusp2 plays a significant role in regulating apoptosis, cell proliferation, metastasis, inflammation, and axon regeneration. The use of KO mouse models and other genetic models has been instrumental in revealing its functions in diseases such as pancreatic cancer, bladder cancer, lupus nephritis, acute kidney injury, and in understanding axon regeneration processes, providing potential therapeutic targets for these diseases.

References:

1. Zhang, Yangyang, Kong, Rui, Yang, Wenbo, Hu, Jisheng, Sun, Bei. 2023. DUSP2 recruits CSNK2A1 to suppress AKT1-mediated apoptosis resistance under hypoxic microenvironment in pancreatic cancer. In Cancer letters, 568, 216288. doi:10.1016/j.canlet.2023.216288. https://pubmed.ncbi.nlm.nih.gov/37390887/

2. Zou, Fan, Rao, Ting, Chen, Wu, Yu, Weimin, Cheng, Fan. 2023. DUSP2 affects bladder cancer prognosis by down-regulating MEK/ERK and P38 MAPK signaling pathways through PTPN7. In Cellular signalling, 112, 110893. doi:10.1016/j.cellsig.2023.110893. https://pubmed.ncbi.nlm.nih.gov/37739277/

3. Xiong, Jiachuan, Ran, Li, Zhu, Yingguo, Zhao, Jinghong, Yang, Ke. 2022. DUSP2-mediated inhibition of tubular epithelial cell pyroptosis confers nephroprotection in acute kidney injury. In Theranostics, 12, 5069-5085. doi:10.7150/thno.72291. https://pubmed.ncbi.nlm.nih.gov/35836796/

4. Shao, Guo-Jian, Wang, Xin-Liang, Wei, Mei-Li, Ren, Da-Long, Hu, Bing. . DUSP2 deletion with CRISPR/Cas9 promotes Mauthner cell axonal regeneration at the early stage of zebrafish. In Neural regeneration research, 18, 577-581. doi:10.4103/1673-5374.350208. https://pubmed.ncbi.nlm.nih.gov/36018180/

5. Yin, Hubin, He, Weiyang, Li, Yunhai, Lin, Yong, Gou, Xin. 2018. Loss of DUSP2 predicts a poor prognosis in patients with bladder cancer. In Human pathology, 85, 152-161. doi:10.1016/j.humpath.2018.11.007. https://pubmed.ncbi.nlm.nih.gov/30458195/