Tet1, short for Tet-eleven translocation 1, is a dioxygenase and 5-methylcytosine hydroxylase belonging to the TET protein family of human α-ketoglutarate oxygenases. It plays a crucial role in decreasing DNA methylation abundance, maintaining DNA methylation-demethylation balance, and regulating gene expression, thus having significant importance in various biological processes like cell differentiation, development, and immunity [3]. It is also involved in pathways such as the NF-κB pathway [1]. Genetic models, especially knockout (KO) mouse models, are valuable tools for studying Tet1.

In Tet1 knockout mice, renal injury, cell death, ROS accumulation, G2/M cell cycle arrest, inflammation, and fibrosis were increased following ischemia-reperfusion or unilateral ureteral obstruction injury, indicating Tet1's role in promoting SOD expression through a DNA-demethylase-dependent mechanism to reduce oxidative stress in acute kidney injury [2]. In 5xFAD mouse model with a Tet1 KO allele, amyloid plaque burden increased, and there were changes in neuropathology, 5hmC, and RNA expression associated with Tet1 loss, suggesting TET1's contribution to Alzheimer's disease pathogenesis [4]. In the context of skeletal stem-cell (SSC) mediated cartilage regeneration, loss of Tet1 in mice skewed the SSC lineage tree, enhanced chondrogenic potential, and in vivo inhibition of TET1 in a mouse model of OA led to increased cartilage regeneration [5].

In conclusion, Tet1 is essential for maintaining DNA methylation homeostasis and regulating gene expression. Model-based research, especially KO mouse models, has revealed its significance in diseases like acute kidney injury, Alzheimer's disease, and osteoarthritis. Understanding Tet1's functions provides insights into the underlying mechanisms of these diseases and may offer potential therapeutic targets.