Tet1-KO Mouse

Tet1, short for ten-eleven translocation 1, is a 5-methylcytosine hydroxylase belonging to the TET protein family of human α-ketoglutarate oxygenases. It plays a crucial role in DNA demethylation, recognizing and binding to CpG islands, thus maintaining the balance of DNA methylation and demethylation for genomic methylation homeostasis and epigenetic regulation [2]. It is involved in various biological processes and associated with multiple pathways, and genetic models are valuable for studying its functions.

In acute kidney injury, Tet1 knockout mice showed increased renal injury, cell death, ROS accumulation, G2/M cell cycle arrest, inflammation, and fibrosis. Tet1 reduces 5mC levels on the promoters of Sod1 and Sod2 to promote their expression, alleviating injury-induced excessive ROS [1]. In cervical cancer cells, TET1 knockdown promoted cell proliferation, migration, invasion, and EMT, while overexpression reversed these processes. TET1 may affect autophagy by altering the methylation levels of NKRF or HIST1H2AK [4]. In Alzheimer's disease, loss of Tet1 in 5xFAD mice increased amyloid plaque burden and led to changes in genes related to neuronal projection organization and dendritic spine development [3]. In a mouse model of OA, Tet1 inhibition enhanced cartilage regeneration by skewing the SSC lineage tree and enhancing chondrogenic potential [5].

In summary, Tet1 is essential for maintaining genomic methylation balance. Through gene knockout models, its role in diseases such as acute kidney injury, cervical cancer, Alzheimer's disease, and osteoarthritis has been revealed. These findings contribute to a better understanding of disease mechanisms and may provide new directions for treatment.

References:

1. Fan, Yu, Yuan, Yangmian, Xiong, Mingrui, Peng, Anlin, Zheng, Ling. 2023. Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase. In Theranostics, 13, 5348-5364. doi:10.7150/thno.87416. https://pubmed.ncbi.nlm.nih.gov/37908721/

2. Liu, Wenzheng, Wu, Guanhua, Xiong, Fei, Chen, Yongjun. 2021. Advances in the DNA methylation hydroxylase TET1. In Biomarker research, 9, 76. doi:10.1186/s40364-021-00331-7. https://pubmed.ncbi.nlm.nih.gov/34656178/

3. Armstrong, Matthew J, Jin, Yulin, Vattathil, Selina M, Wingo, Thomas S, Jin, Peng. 2023. Role of TET1-mediated epigenetic modulation in Alzheimer's disease. In Neurobiology of disease, 185, 106257. doi:10.1016/j.nbd.2023.106257. https://pubmed.ncbi.nlm.nih.gov/37562656/

4. Ren, Ji, Chen, Xiuying, Li, Jing, Tan, Yujie, Ding, Yan. 2024. TET1 inhibits the migration and invasion of cervical cancer cells by regulating autophagy. In Epigenetics, 19, 2323751. doi:10.1080/15592294.2024.2323751. https://pubmed.ncbi.nlm.nih.gov/38431880/

5. Pandey, Akshay, Hoover, Malachia, Singla, Mamta, Chan, Charles, Bhutani, Nidhi. 2023. TET1 Regulates Skeletal Stem-Cell Mediated Cartilage Regeneration. In Arthritis & rheumatology (Hoboken, N.J.), 76, 216-230. doi:10.1002/art.42678. https://pubmed.ncbi.nlm.nih.gov/37610277/