Zbtb7b-KO Mouse

Zbtb7b, also known as Th-inducing POZ-Kruppel factor (ThPOK), is a transcription factor with diverse functions. It is involved in multiple biological pathways, including those related to cell differentiation, inflammation, and lipid metabolism, and is of great biological importance in various tissues and disease contexts. Gene knockout (KO) and conditional knockout (CKO) mouse models have been crucial in understanding its functions [1,3].

In hepatocarcinogenesis, hepatocyte-specific ZBTB7B knockout in mouse models shows that ZBTB7B deficiency promotes HCC development by down-regulating adult liver-specific gene expression, priming livers to a fetal-like state, and up-regulating c-Jun, a key molecule in liver cancer initiation [1]. In metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC, Zbtb7b knockout in mice reveals its role in compensating for lipid deposition during MASLD progression. Zbtb7b suppresses H19-mediated hepatic lipid deposition, reducing HCC cell proliferation and migration [3]. In radiation-induced lung injury, silencing Zbtb7b in cells leads to higher radiation-induced IL-6 production, indicating its role in suppressing aseptic inflammation by regulating m6A modification of IL6 mRNA [2].

In conclusion, Zbtb7b serves as a significant regulator in multiple biological processes and disease conditions. Mouse KO/CKO models have been instrumental in uncovering its functions in diseases such as HCC, MASLD-related HCC, and radiation-induced lung injury, highlighting its potential as a therapeutic target for these diseases.

References:

1. Zhu, Yue, Wang, Qinqin, Xie, Xinyu, Li, Chen, Ge, Gaoxiang. 2024. ZBTB7B is a permissive regulator of hepatocellular carcinoma initiation by repressing c-Jun expression and function. In Cell death & disease, 15, 55. doi:10.1038/s41419-024-06441-y. https://pubmed.ncbi.nlm.nih.gov/38225233/

2. Zhao, Jun, Han, Dun-Xin, Wang, Chun-Bo, Wang, Xi-Lin. 2020. Zbtb7b suppresses aseptic inflammation by regulating m6A modification of IL6 mRNA. In Biochemical and biophysical research communications, 530, 336-341. doi:10.1016/j.bbrc.2020.07.011. https://pubmed.ncbi.nlm.nih.gov/32828308/

3. Han, Yinglin, Wu, Kaimin, Peng, Xin, Jiang, He, Zhao, Xu-Yun. . Zbtb7b defines a compensatory mechanism in MASLD-related HCC progression by suppressing H19-mediated hepatic lipid deposition. In Physiological reports, 12, e70160. doi:10.14814/phy2.70160. https://pubmed.ncbi.nlm.nih.gov/39714087/