Isoc1-KO Mouse

Isoc1, short for Isochorismatase domain-containing 1, is a gene with an isochorismatase domain, though its precise functions in humans were initially unclear. It has been implicated in multiple biological processes and disease-related pathways, including inflammation, cell proliferation, apoptosis, and DNA damage repair [1-7].

In macrophages, Isoc1 deficiency led to a significant increase in the production of inflammatory cytokines. This was found to be due to the activation of AKT1, which reduced the stability of PEX11B, affecting peroxisome biogenesis and thus inflammation [1]. In cancer research, Isoc1 showed different roles in various cancers. In hepatocellular carcinoma, its down-regulation was associated with poor prognosis, and overexpression inhibited cell proliferation, migration, and invasion [2]. Conversely, in gastric cancer, Isoc1 was up-regulated and promoted cell proliferation by positively regulating CDK19 [3]. In colon, pancreatic, and lung cancers, knockdown of Isoc1 inhibited cell proliferation, migration, and invasion, and induced apoptosis [4-6]. In Th1* memory cells, depletion of Isoc1 impaired IFN-γ and IL-17 production, along with defects in oxidative phosphorylation, glycolysis, and pyrimidine metabolism [4].

In conclusion, Isoc1 plays crucial roles in inflammation regulation and cancer-related biological processes. Gene-knockout and other loss-of-function experiments, though not always in KO/CKO mouse models, have revealed its significance in these areas. Understanding Isoc1's functions provides insights into the mechanisms of inflammation-related diseases and cancer development, potentially guiding new therapeutic strategies [1-9].

References:

1. Lin, Xiaoyuan, Zhao, Qingting, Fu, Beibei, Xu, Shiyao, Wu, Haibo. 2022. ISOC1 Modulates Inflammatory Responses in Macrophages through the AKT1/PEX11B/Peroxisome Pathway. In Molecules (Basel, Switzerland), 27, . doi:10.3390/molecules27185896. https://pubmed.ncbi.nlm.nih.gov/36144632/

2. Xiang, Jiao, Gao, Xiao-Qiang, Chen, Xiang-Ling, Lu, Yin-Ying. 2021. ISOC1 is a novel potential tumor suppressor in hepatocellular carcinoma. In Neoplasma, 69, 174-182. doi:10.4149/neo_2021_210815N1157. https://pubmed.ncbi.nlm.nih.gov/34846160/

3. Zhao, J-Q, Li, X-N, Fu, L-P, Zhang, N, Cai, J-H. . ISOC1 promotes the proliferation of gastric cancer cells by positively regulating CDK19. In European review for medical and pharmacological sciences, 24, 11602-11609. doi:10.26355/eurrev_202011_23803. https://pubmed.ncbi.nlm.nih.gov/33275227/

4. Kushnareva, Yulia, Mathews, Ian T, Andreyev, Alexander Y, Peters, Bjoern, Sharma, Sonia. 2021. Functional Analysis of Immune Signature Genes in Th1* Memory Cells Links ISOC1 and Pyrimidine Metabolism to IFN-γ and IL-17 Production. In Journal of immunology (Baltimore, Md. : 1950), 206, 1181-1193. doi:10.4049/jimmunol.2000672. https://pubmed.ncbi.nlm.nih.gov/33547171/