Carm1-flox Mouse

CARM1, also known as coactivator-associated arginine methyltransferase 1, is an arginine methyltransferase. It post-translationally modifies various proteins, including histones, transcription factors, and splicing factors, regulating multiple levels of RNA production and processing. It is involved in pathways such as transcription regulation, cell cycle control, and metabolism, and is of great biological importance in processes like development, autophagy, and tumorigenesis. Genetic models, especially KO/CKO mouse models, have been valuable in studying its functions [5].

In osteoporosis, CARM1 KO in vitro showed that it reprograms glucose metabolism in osteoblasts and osteoclasts, promoting osteogenic differentiation and inhibiting osteoclastic differentiation, and in vivo it decreased bone loss in osteoporosis model mice. Mechanistically, it methylates PPP1CA, affecting AKT-T450 and AMPK-T172 dephosphorylation and regulating glycolytic and oxidative phosphorylation fluxes [1].

In triple-negative breast cancer, CARM1 promotes proliferation, epithelial-mesenchymal transition, and stemness. Genome-wide analysis showed its recruitment by HIF1A to occupy promoters of key genes. Ellagic acid, an inhibitor of CARM1, can suppress TNBC cell proliferation and invasion [2].

In autophagy, nutrient starvation-induced AMPK-dependent phosphorylation of FOXO3a represses SKP2, increasing CARM1 protein levels and histone H3 Arg17 dimethylation, and CARM1 acts as a transcriptional co-activator on autophagy-related genes [3].

In colorectal cancer, inhibition of CARM1-mediated methylation of ACSL4 promotes ferroptosis both in vitro and in vivo [4].

In breast cancer, CARM1 hypermethylates the NuRD chromatin remodeling complex to promote cell cycle gene expression and cancer development, and targeting CARM1-mediated GATAD2A/2B methylation inhibits breast cancer cell growth [6].

In skeletal muscle, CARM1-specific knockout in mice led to lower muscle mass, dysregulated autophagic and atrophic signaling, decreased mitophagy and autophagy flux, and disrupted fasting-induced muscle atrophy [7].

In conclusion, CARM1 is crucial in various biological processes and diseases. KO/CKO mouse models have revealed its roles in osteoporosis, breast cancer, autophagy, colorectal cancer, and skeletal muscle atrophy. It regulates metabolism, cell cycle, autophagy, and other processes, highlighting its potential as a therapeutic target in related diseases.