Zbtb16-KO Mouse

Zbtb16, also known as zinc-finger and BTB domain-containing protein 16, functions as a transcription factor and is involved in multiple biological processes. It participates in pathways related to osteogenesis, cell cycle regulation, inflammation, and cell differentiation. Its biological importance spans various tissues and diseases, highlighting its significance in maintaining normal physiological functions [1,2,3,4,5].

In osteogenesis, super enhancers (SEs) target Zbtb16, which promotes mesenchymal stem cell (MSC) osteogenesis. SEs recruit BRD4 to the Zbtb16 site, which then binds to RPAP2, facilitating Zbtb16 transcriptional elongation via SP7 and protecting against osteoporosis. In nasopharyngeal carcinoma, KDM5B inhibits Zbtb16 expression, leading to increased TOP2A expression and cisplatin resistance. Inflammasome activity is modulated by Zbtb16-dependent SUMOylation of ASC, reducing acute inflammatory pathogenesis in a mouse model of Muckle-Wells syndrome. In lung adenocarcinoma, Zbtb16 inhibits DNA replication and induces cell cycle arrest by targeting WDHD1 transcription. Deletion of Zbtb16 in mice causes social and cognitive impairments, along with neocortical developmental defects [1,2,3,5,6].

In summary, Zbtb16 plays crucial roles in osteogenesis, cancer development, inflammation, and neural development. Gene knockout and conditional knockout mouse models have been instrumental in revealing these functions, contributing to our understanding of diseases such as osteoporosis, nasopharyngeal carcinoma, inflammatory diseases, lung adenocarcinoma, and neurodevelopmental disorders [1,2,3,5,6].

References:

1. Yu, Wenhui, Xie, Zhongyu, Li, Jinteng, Wu, Yanfeng, Shen, Huiyong. 2023. Super enhancers targeting ZBTB16 in osteogenesis protect against osteoporosis. In Bone research, 11, 30. doi:10.1038/s41413-023-00267-8. https://pubmed.ncbi.nlm.nih.gov/37280207/

2. Zhang, Bin, Li, Jie, Wang, Yijun, Li, Yan, Yang, Kunyu. 2024. Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis. In Cell death and differentiation, 31, 309-321. doi:10.1038/s41418-024-01257-x. https://pubmed.ncbi.nlm.nih.gov/38287116/

3. Dong, Danfeng, Du, Yuzhang, Fei, Xuefeng, Sadler, Anthony, Xu, Dakang. 2023. Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC. In Nature communications, 14, 8465. doi:10.1038/s41467-023-43945-1. https://pubmed.ncbi.nlm.nih.gov/38123560/

4. Šeda, O, Šedová, L, Včelák, J, Liška, F, Bendlová, B. . ZBTB16 and metabolic syndrome: a network perspective. In Physiological research, 66, S357-S365. doi:. https://pubmed.ncbi.nlm.nih.gov/28948820/

5. Wang, Kai, Guo, Deyu, Yan, Tao, Wang, Guanghui, Du, Jiajun. 2024. ZBTB16 inhibits DNA replication and induces cell cycle arrest by targeting WDHD1 transcription in lung adenocarcinoma. In Oncogene, 43, 1796-1810. doi:10.1038/s41388-024-03041-0. https://pubmed.ncbi.nlm.nih.gov/38654107/

6. Usui, Noriyoshi, Berto, Stefano, Konishi, Ami, Matsuzaki, Hideo, Shimada, Shoichi. 2021. Zbtb16 regulates social cognitive behaviors and neocortical development. In Translational psychiatry, 11, 242. doi:10.1038/s41398-021-01358-y. https://pubmed.ncbi.nlm.nih.gov/33895774/