Inmt-KO Mouse

Inmt, or indolethylamine N-methyltransferase, is a transmethylation enzyme. It uses the methyl donor S-adenosyl-L-methionine to transfer methyl groups to amino groups of small molecule acceptor compounds. It is well-known for its role in the biosynthesis of N,N-Dimethyltryptamine (DMT), a psychedelic compound present in mammalian brain and other tissues [1].

A study generating an INMT-knockout rat model found that brain and lung tissues from both wild-type and INMT-knockout rats had equal levels of tryptamine-dependent activity, but the enzymatic products were neither N-methyltryptamine (NMT) nor DMT. Rat INMT was also insufficient for NMT or DMT biosynthesis, suggesting an alternative enzymatic pathway for DMT biosynthesis in rats [1]. In prostate cancer, high INMT expression is associated with castration-resistant prostate cancer (CRPC). Knockdown of INMT or treatment with its inhibitor suppressed CRPC development, indicating INMT promotes PCa castration resistance via detoxification of anticancer metabolites [2]. In lung adenocarcinoma, low INMT expression is associated with poor prognosis but favorable immunotherapy response. Gene set enrichment analysis showed cell cycle and DNA damage response pathways were enriched in the INMT low-expression group [3]. In head and neck squamous cell carcinoma (HNSC), low INMT expression is related to poor overall survival, hypomethylation, and immune infiltration [4].

In conclusion, Inmt plays a role in DMT biosynthesis and is associated with various diseases. The INMT-knockout rat model helped reveal its non-essential role in endogenous tryptamine-dependent methylation activity in rats. In cancer research, understanding Inmt's function through loss-of-function studies provides potential therapeutic strategies for CRPC, lung adenocarcinoma, and HNSC.

References:

1. Glynos, Nicolas G, Carter, Lily, Lee, Soo Jung, Wang, Michael M, Borjigin, Jimo. 2023. Indolethylamine N-methyltransferase (INMT) is not essential for endogenous tryptamine-dependent methylation activity in rats. In Scientific reports, 13, 280. doi:10.1038/s41598-023-27538-y. https://pubmed.ncbi.nlm.nih.gov/36609666/

2. Zhong, Shangwei, Jeong, Ji-Hak, Huang, Changhao, Yang, Li, Luo, Jun-Li. 2021. Targeting INMT and interrupting its methylation pathway for the treatment of castration resistant prostate cancer. In Journal of experimental & clinical cancer research : CR, 40, 307. doi:10.1186/s13046-021-02109-z. https://pubmed.ncbi.nlm.nih.gov/34587977/

3. Zhou, Xincheng, Zou, Bing, Wang, Jian, Tan, Qiang, Ji, Chunyu. 2022. Low expression of INMT is associated with poor prognosis but favorable immunotherapy response in lung adenocarcinoma. In Frontiers in genetics, 13, 946848. doi:10.3389/fgene.2022.946848. https://pubmed.ncbi.nlm.nih.gov/36437916/

4. Cui, Kun, Yao, Xi, Wei, Zhengbo, Tang, Jinping, Xie, Ying. 2022. Poor prognosis, hypomethylation, and immune infiltrates are associated with downregulation of INMT in head and neck squamous cell carcinoma. In Frontiers in genetics, 13, 917344. doi:10.3389/fgene.2022.917344. https://pubmed.ncbi.nlm.nih.gov/36186458/