As3mt-KO Mouse

As3mt, also known as arsenic (3) methyltransferase, is a key enzyme in arsenic metabolism. It catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to trivalent arsenical, participating in the methylation steps of inorganic arsenic (iAs) metabolism, which forms methylated arsenite and other metabolites [2,3]. This process is crucial as arsenic exposure is linked to various health issues, and As3mt is involved in related pathways that impact health. Genetic models, like humanized mouse models, are valuable for studying its functions.

In arsenic-induced non-alcoholic fatty liver disease (NAFLD), As3mt plays a significant role. Chronic arsenic exposure increases As3mt levels, and it blocks m6A-mediated miR-142-5p maturation by consuming SAM. This leads to elevated levels of SREBP1 and lipogenic genes, causing liver steatosis. SAM supplementation or As3mt deficiency can block arsenic-induced lipid accumulation by promoting miR-142-5p maturation [1]. In humanized As3mt mice exposed to arsenic, sex divergence in diabetes-related markers was detected, suggesting that humanized males may be at increased risk for metabolic dysfunction [4].

In conclusion, As3mt is essential for arsenic metabolism. Model-based research, especially with mouse models, has revealed its role in diseases such as NAFLD and arsenic-related metabolic diseases. Understanding As3mt provides insights into the mechanisms of arsenic-induced diseases, potentially offering new strategies for prevention and treatment.

References:

1. Li, Han, Wu, Lu, Ye, Fuping, Zhang, Aihua, Liu, Qizhan. 2023. As3MT via consuming SAM is involved in arsenic-induced nonalcoholic fatty liver disease by blocking m6A-mediated miR-142-5p maturation. In The Science of the total environment, 892, 164746. doi:10.1016/j.scitotenv.2023.164746. https://pubmed.ncbi.nlm.nih.gov/37301390/

2. Mersaoui, Sofiane Y, Guilbert, Cynthia, Chou, Hsiang, Richard, Stéphane, Mann, Koren K. 2022. Arsenic 3 methyltransferase (AS3MT) automethylates on cysteine residues in vitro. In Archives of toxicology, 96, 1371-1386. doi:10.1007/s00204-022-03248-8. https://pubmed.ncbi.nlm.nih.gov/35244730/

3. Agusa, Tetsuro, Fujihara, Junko, Takeshita, Haruo, Iwata, Hisato. 2011. Individual variations in inorganic arsenic metabolism associated with AS3MT genetic polymorphisms. In International journal of molecular sciences, 12, 2351-82. doi:10.3390/ijms12042351. https://pubmed.ncbi.nlm.nih.gov/21731446/

4. Todero, Jenna, Douillet, Christelle, Shumway, Alexandria J, Stýblo, Miroslav, Sethupathy, Praveen. 2023. Molecular and Metabolic Analysis of Arsenic-Exposed Humanized AS3MT Mice. In Environmental health perspectives, 131, 127021. doi:10.1289/EHP12785. https://pubmed.ncbi.nlm.nih.gov/38150313/