As3mt-KO Mouse

As3mt, also known as arsenic (3) methyltransferase, is a key enzyme involved in the methylation metabolism of arsenic. It catalyzes the transfer of a methyl group from S-adenosyl-l-methionine (AdoMet) to trivalent arsenical, playing a role in arsenic metabolism pathways [2,3]. This process is crucial as arsenic exposure is associated with various health issues, making As3mt an important factor in understanding arsenic-related biological effects. Genetic models, such as mouse models, can be valuable for studying its functions.

In arsenic-induced non-alcoholic fatty liver disease (NAFLD), chronic arsenic exposure increased As3mt levels in mice. As3mt, by consuming SAM, blocked m6A-mediated miR-142-5p maturation, leading to elevated levels of SREBP1 and lipogenic genes, and ultimately causing liver steatosis. SAM supplementation or As3mt deficiency blocked arsenic-induced lipid accumulation by promoting miR-142-5p maturation [1]. In humanized As3mt mice exposed to inorganic arsenic, sex-specific differences in diabetes-related markers were detected, with humanized males at increased risk for metabolic dysfunction [4].

In conclusion, As3mt is essential in arsenic metabolism. Studies using gene-modified mouse models have revealed its role in arsenic-related diseases like NAFLD and metabolic dysfunction, highlighting its importance in understanding the mechanisms underlying these diseases and potentially guiding future treatment strategies related to arsenic-induced pathologies.

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. Antonelli, Ray, Shao, Kan, Thomas, David J, Sams, Reeder, Cowden, John. 2014. AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility. In Environmental research, 132, 156-67. doi:10.1016/j.envres.2014.03.012. https://pubmed.ncbi.nlm.nih.gov/24792412/

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/