Ahcy-KO Mouse

Ahcy, also known as adenosylhomocysteinase, is a highly conserved enzyme in living organisms. It catalyzes the reversible breakdown of S-adenosylhomocysteine (SAH), a by-product and potent inhibitor of methyltransferases activity. This function is crucial for maintaining normal methyltransferase activity and thus plays a key role in the methionine cycle, which is involved in DNA, RNA, and histone methylation processes [1].

In mouse models, inhibition of Ahcy using adenosine dialdehyde (AdOx) or gene-specific siRNAs in adipocyte progenitor cells (APCs) reduced APC proliferation and number, and further inhibited their differentiation into mature adipocytes [2]. In colorectal cancer, targeting Ahcy function impaired the growth of APC-deficient organoids in vitro and prevented the hyperproliferative phenotype in vivo. Pharmacological inhibition of Ahcy also reduced intestinal tumour burden in ApcMin/+ mice, indicating its potential as a metabolic drug target in CRC [3].

In conclusion, Ahcy is essential for normal cellular methylation processes, as demonstrated by its impact on cell proliferation and differentiation in adipocytes and its role in colorectal cancer. The study of Ahcy using mouse models has provided valuable insights into its function in specific biological processes and disease conditions, suggesting potential therapeutic strategies related to methylation-associated diseases.

References:

1. Vizán, Pedro, Di Croce, Luciano, Aranda, Sergi. 2021. Functional and Pathological Roles of AHCY. In Frontiers in cell and developmental biology, 9, 654344. doi:10.3389/fcell.2021.654344. https://pubmed.ncbi.nlm.nih.gov/33869213/

2. Boczki, Paula, Colombo, Marco, Weiner, Juliane, Körner, Antje, Landgraf, Kathrin. 2023. Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells. In Adipocyte, 13, 2290218. doi:10.1080/21623945.2023.2290218. https://pubmed.ncbi.nlm.nih.gov/38064408/

3. Vande Voorde, Johan, Steven, Rory T, Najumudeen, Arafath K, Bunch, Josephine, Sansom, Owen J. 2023. Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target. In Nature metabolism, 5, 1303-1318. doi:10.1038/s42255-023-00857-0. https://pubmed.ncbi.nlm.nih.gov/37580540/