Prmt7-KO Mouse

Prmt7, a type III protein arginine methyltransferase, is a unique member of the PRMT family. It solely catalyzes the formation of ω-monomethylarginine, playing pivotal roles in many biological processes such as regulating gene expression, DNA repair, RNA splicing, and stem cell biology [2]. Protein arginine methylation, catalyzed by PRMTs, is a post-translational modification that impacts protein-protein and protein-nucleic acid interactions [5].

Genetic loss of Prmt7 in a CML mouse model delayed leukemia development and impaired self-renewal of leukemia stem cells (LSCs) without affecting normal hematopoiesis. Mechanistically, it led to reduced expression of glycine decarboxylase, reprogramming glycine metabolism to generate methylglyoxal, detrimental to LSCs [1]. Mouse Prmt7 homozygous knockouts showed defects in muscle stem cells and immune cells, while humans lacking Prmt7 had significant intellectual developmental delays, hypotonia, and facial dysmorphisms [2]. In a melanoma mouse model, PRMT7-deficient B16.F10 melanoma increased immune cell infiltration, restraining tumor growth [3]. In postmenopausal cardiomyopathy, cardiac-specific Prmt7 ablation in mice showed sex-specific cardiomyopathy phenotypes, and Prmt7 was found to regulate the JAK/STAT/Socs3 signaling pathway [4].

In conclusion, Prmt7 is crucial for multiple biological functions, with its deficiency or mutation causing various developmental and functional abnormalities. Mouse knockout models have been instrumental in revealing its roles in diseases like CML, melanoma, and postmenopausal cardiomyopathy, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Liu, Chang, Zou, Waiyi, Nie, Danian, Jin, Yanli, Pan, Jingxuan. 2022. Loss of PRMT7 reprograms glycine metabolism to selectively eradicate leukemia stem cells in CML. In Cell metabolism, 34, 818-835.e7. doi:10.1016/j.cmet.2022.04.004. https://pubmed.ncbi.nlm.nih.gov/35508169/

2. Jain, Kanishk, Clarke, Steven G. 2019. PRMT7 as a unique member of the protein arginine methyltransferase family: A review. In Archives of biochemistry and biophysics, 665, 36-45. doi:10.1016/j.abb.2019.02.014. https://pubmed.ncbi.nlm.nih.gov/30802433/

3. Srour, Nivine, Villarreal, Oscar D, Hardikar, Swanand, Del Rincón, Sonia V, Richard, Stéphane. . PRMT7 ablation stimulates anti-tumor immunity and sensitizes melanoma to immune checkpoint blockade. In Cell reports, 38, 110582. doi:10.1016/j.celrep.2022.110582. https://pubmed.ncbi.nlm.nih.gov/35354055/

4. Ahn, Byeong-Yun, Zhang, Yan, Wei, Shibo, Leem, Young-Eun, Kang, Jong-Sun. 2024. Prmt7 regulates the JAK/STAT/Socs3 signaling pathway in postmenopausal cardiomyopathy. In Experimental & molecular medicine, 56, 711-720. doi:10.1038/s12276-024-01193-3. https://pubmed.ncbi.nlm.nih.gov/38486105/

5. Halabelian, Levon, Barsyte-Lovejoy, Dalia. 2021. Structure and Function of Protein Arginine Methyltransferase PRMT7. In Life (Basel, Switzerland), 11, . doi:10.3390/life11080768. https://pubmed.ncbi.nlm.nih.gov/34440512/