Mettl5-flox Mouse

METTL5, an N6-adenosine methyltransferase, is crucial for 18S rRNA m6A modification. This modification is involved in multiple biological processes, such as ribosome synthesis, mRNA translation, and cell metabolism regulation. It also plays a role in various pathways including those related to cancer development and craniofacial development [3,4].

In cancer research, METTL5 has been found to be a key player. In hepatocellular carcinoma (HCC), METTL5 promotes glucose metabolic reprogramming, cell proliferation, and metastasis by stabilizing c-Myc through facilitating USP5 translation [1]. In intrahepatic cholangiocarcinoma (ICC), METTL5-mediated 18S rRNA m6A modification promotes oncogenic mRNA translation and tumor progression [2]. In gastric cancer, METTL5 promotes tumor development via sphingomyelin metabolism and confers cisplatin resistance [5]. In nonsmall cell lung cancer (NSCLC), METTL5 promotes cancer cell proliferation by interacting with IGF2BP3 [7]. In addition, in a mouse model, deletion of Mettl5 leads to poor ossification, widened cranial sutures, and a cleidocranial dysplasia-like phenotype, with Wnt signaling significantly downregulated, indicating its role in craniofacial development [6].

In conclusion, METTL5 is essential for 18S rRNA m6A modification, which impacts multiple biological processes. Its dysregulation is closely associated with various cancers and craniofacial development disorders. Gene knockout and conditional knockout mouse models have been instrumental in revealing these functions, providing potential therapeutic targets for related diseases.