Tmt1a-flox Mouse

Tmt1a, formerly known as METTL7A, is a thiol methyltransferase. It can methylate and inactivate histone deacetylase inhibitors (HDACis) with a thiol as the zinc-binding group, mediating resistance to these drugs [1,2]. It belongs to the METTL7 family and is responsible for alkyl S-thiol methyl transferase activity in the liver, which is crucial for the S-methylation of drugs containing thiol-moieties, altering their activity and leading to detoxification [3].

Research has shown that Tmt1a is conserved across different species, such as rats, mice, chickens, and zebrafish, with varying degrees of amino acid sequence identity to human Tmt1a. Cells transfected to express homologs of Tmt1a from these species conferred resistance to thiol-based HDACIs, blunted the downstream effects of HDACi treatment, and increased the levels of dimethylated romidepsin, indicating that the molecule-methylating ability of Tmt1a is conserved across species. This conservation suggests that animal models could be useful for elucidating its role in humans [1,2].

In conclusion, Tmt1a is an important thiol methyltransferase involved in drug resistance to certain HDACis and drug metabolism in the liver. The conservation of its function across species, as demonstrated in the studies, implies that animal models can potentially contribute to understanding its role in human biological processes and disease-related mechanisms, especially in relation to HDACi-mediated therapies [1,2,3].