Alkbh5-flox Mouse

Alkbh5, short for Alkylation Repair Homolog Protein 5, is an RNA N6 -methyladenosine (m6A) demethylase. The m6A modification is a prevalent epigenetic modification in RNA, and Alkbh5 -mediated m6A demethylation can regulate gene expression by influencing multiple RNA metabolic events like pre -mRNA processing, mRNA decay, and translation. It is involved in various biological processes and is of great significance in maintaining normal physiological functions and understanding disease mechanisms [4].

In mice, macrophage-specific knockout of Alkbh5 inhibits angiotensin II-induced macrophage-to-myofibroblast transition, alleviating cardiac fibrosis and dysfunction, suggesting its role in hypertensive cardiac fibrosis [1]. Selective deletion of Alkbh5 in astrocytes produces antidepressant-like behaviors, indicating its contribution to depressive-like behaviors [2]. Hepatocyte-specific deletion of Alkbh5 reduces glucose and lipids by inhibiting the glucagon receptor (GCGR) and mammalian target of rapamycin complex 1 (mTORC1) signaling pathways, highlighting its role in glucose and lipid homeostasis [3]. In addition, Alkbh5 knockout in mesenchymal stem cells (MSCs) aggravates spontaneous osteoarthritis in mice, while its overexpression improves the efficacy of MSCs in osteoarthritis, revealing its function in MSC senescence and osteoarthritis progression [5]. Also, Alkbh5-knockout mice exhibit milder pathological damage and better renal function than wild-type mice post-ischemia-reperfusion injury (IRI), and conditional knockout of Alkbh5 in tubular epithelial cells alleviates I/R-induced acute kidney injury (AKI) and fibrosis [6].

In conclusion, Alkbh5 is a crucial RNA m6A demethylase involved in multiple biological processes. Gene knockout and conditional knockout mouse models have significantly contributed to revealing its roles in diseases such as cardiac fibrosis, depression, metabolic diseases, osteoarthritis, and AKI. These findings provide potential therapeutic targets for treating related diseases.