Impdh1-KO Mouse

Impdh1, or inosine monophosphate dehydrogenase 1, is a key regulatory enzyme in the de novo synthesis of the purine base guanine. It plays a crucial role in the GTP biosynthesis pathway, and its function is essential for various biological processes such as nucleotide metabolism [1,2].

Mutations in Impdh1 are causative for RP10 autosomal dominant retinitis pigmentosa (adRP), presenting most frequently in the first decade of life with early macular involvement [1]. In cancer research, it has been found that Impdh1 is highly upregulated in colorectal cancer and promotes its growth in vitro and in vivo. The c-Myc-Impdh1/2 axis promotes tumourigenesis by regulating GTP metabolic reprogramming, and Impdh1 may be a potential combined target of immunotherapy [2,3]. In clear cell renal cell carcinoma (ccRCC), Impdh1 forms a positive feedback loop with Y-box binding protein 1 (YB-1), and their interaction is related to tumour metastasis [4]. Also, in gliomas, a lower ratio of Impdh1 to Impdh2 sensitizes gliomas to chemotherapy [5].

In conclusion, Impdh1 is vital for purine and GTP biosynthesis. Its dysregulation is associated with multiple diseases, especially retinitis pigmentosa and various cancers. Research on Impdh1 in these disease models helps to understand the underlying disease mechanisms and could potentially lead to the development of new therapeutic strategies.

References:

1. Sakti, Dhimas H, Cornish, Elisa E, Nash, Benjamin M, Jamieson, Robyn V, Grigg, John R. 2023. IMPDH1-associated autosomal dominant retinitis pigmentosa: natural history of novel variant Lys314Gln and a comprehensive literature search. In Ophthalmic genetics, 44, 437-455. doi:10.1080/13816810.2023.2215310. https://pubmed.ncbi.nlm.nih.gov/37259572/

2. Zhang, Qiang, Cui, Kaisa, Yang, Xiaoya, He, Zhen, Lan, Ping. . c-Myc-IMPDH1/2 axis promotes tumourigenesis by regulating GTP metabolic reprogramming. In Clinical and translational medicine, 13, e1164. doi:10.1002/ctm2.1164. https://pubmed.ncbi.nlm.nih.gov/36629054/

3. Liu, Chengdong, Zhang, Wanli, Zhou, Xiaohan, Liu, Li. 2022. IMPDH1, a prognostic biomarker and immunotherapy target that correlates with tumor immune microenvironment in pan-cancer and hepatocellular carcinoma. In Frontiers in immunology, 13, 983490. doi:10.3389/fimmu.2022.983490. https://pubmed.ncbi.nlm.nih.gov/36618420/

4. Ruan, Hailong, Song, Zhengshuai, Cao, Qi, Zhang, Xiaoping, Chen, Ke. 2020. IMPDH1/YB-1 Positive Feedback Loop Assembles Cytoophidia and Represents a Therapeutic Target in Metastatic Tumors. In Molecular therapy : the journal of the American Society of Gene Therapy, 28, 1299-1313. doi:10.1016/j.ymthe.2020.03.001. https://pubmed.ncbi.nlm.nih.gov/32209435/

5. Ruan, Xiaoyu, Xiong, Yundong, Li, Xiaoman, Yang, Ence, Wang, Jiadong. 2024. Lower ratio of IMPDH1 to IMPDH2 sensitizes gliomas to chemotherapy. In Cancer gene therapy, 31, 1081-1089. doi:10.1038/s41417-024-00793-5. https://pubmed.ncbi.nlm.nih.gov/38871858/