Ifng-KO Mouse

Ifng, encoding Interferon gamma, is a key cytokine in the immune system. It plays a vital role in augmenting immune function, for instance, promoting the maturation of innate immune cells [2]. It is involved in various immune-related pathways such as the JAK-STAT signaling pathway [3]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In autism spectrum disorder (ASD), real-time PCR analysis showed significant up-regulation of IFNG in children with ASD compared to controls, suggesting a functional disruption in the IFNG/IFNG-AS1 regulatory network, which may contribute to the chronic inflammatory aspect of ASD [1]. In colon adenocarcinoma (COAD), IFNG was significantly correlated with tumor immunotherapy biomarkers, and its high expression was associated with longer disease-free survival. Also, autophagy and IFNG were related to cisplatin chemosensitivity, indicating IFNG could be a potential targeted therapy for cisplatin-resistant colon cancer [3]. In tuberculosis, IFNG gene polymorphisms were associated with the disease in the Tibetan population. For example, rs1861494 CT was a protective factor against TB compared with TT genotype [4]. Another study found that the IFNG rs1861494 allele C was related to an increased risk for TB, especially in younger and male subgroups [6]. In pancreatic cancer, CDK1/2/5 inactivation blocked IFNG-induced immune checkpoint expression and triggered immunogenic cell death, overcoming IFNG-mediated adaptive immune resistance [5].

In conclusion, Ifng is crucial for immune function and is involved in multiple disease conditions. Studies using gene knockout or other genetic models have revealed its role in ASD, COAD, tuberculosis, and pancreatic cancer, among others. These findings help in understanding disease mechanisms and potentially developing new therapeutic strategies.

References:

1. Fallah, Hamid, Sayad, Arezou, Ranjbaran, Fatemeh, Ghafouri-Fard, Soudeh, Taheri, Mohammad. 2019. IFNG/IFNG-AS1 expression level balance: implications for autism spectrum disorder. In Metabolic brain disease, 35, 327-333. doi:10.1007/s11011-019-00510-4. https://pubmed.ncbi.nlm.nih.gov/31728886/

2. Benci, Joseph L, Johnson, Lexus R, Choa, Ruth, Kambayashi, Taku, Minn, Andy J. . Opposing Functions of Interferon Coordinate Adaptive and Innate Immune Responses to Cancer Immune Checkpoint Blockade. In Cell, 178, 933-948.e14. doi:10.1016/j.cell.2019.07.019. https://pubmed.ncbi.nlm.nih.gov/31398344/

3. Yue, Taohua, Cai, Yunlong, Zhu, Jing, Wang, Pengyuan, Rong, Long. 2023. Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients. In Frontiers in immunology, 14, 1064704. doi:10.3389/fimmu.2023.1064704. https://pubmed.ncbi.nlm.nih.gov/36756126/

4. Wu, S-Q, Ding, X-J, Yang, Q-L, Wang, M-G, He, J-Q. . IFNG and IFNGR1 polymorphisms are associated with tuberculosis: a case-control study. In European review for medical and pharmacological sciences, 26, 8777-8787. doi:10.26355/eurrev_202212_30549. https://pubmed.ncbi.nlm.nih.gov/36524496/

5. Huang, Jin, Chen, Pan, Liu, Ke, Kang, Rui, Tang, Daolin. 2020. CDK1/2/5 inhibition overcomes IFNG-mediated adaptive immune resistance in pancreatic cancer. In Gut, 70, 890-899. doi:10.1136/gutjnl-2019-320441. https://pubmed.ncbi.nlm.nih.gov/32816920/

6. Wu, Shouquan, Wang, Yu, Zhang, Miaomiao, Wang, Minggui, He, Jian-Qing. 2019. Genetic variants in IFNG and IFNGR1 and tuberculosis susceptibility. In Cytokine, 123, 154775. doi:10.1016/j.cyto.2019.154775. https://pubmed.ncbi.nlm.nih.gov/31310896/