Zbtb16, also known as zinc-finger and BTB domain-containing protein 16, is a transcription factor that plays diverse roles in various biological processes. It is involved in pathways related to osteogenesis, cell cycle regulation, and immune response, among others. Genetic models, especially KO/CKO mouse models, have been crucial in understanding its functions.

In osteogenesis, super enhancers targeting Zbtb16 are essential for mesenchymal stem cell (MSC) osteogenesis. Deletion of Brd4, which is involved in Zbtb16 transcriptional regulation, in Brd4fl/fl Prx1-cre mice leads to decreased bone density and remodeling capacity, and bone-targeting Zbtb16 overexpression has a therapeutic effect on osteoporosis models [1].

In nasopharyngeal carcinoma, KDM5B overexpression inhibits Zbtb16 expression, increasing Topoisomerase II-α (TOP2A) and conferring cisplatin resistance. Deletion of USP7, which stabilizes KDM5B, increases cisplatin sensitivity [2].

In lung adenocarcinoma, Zbtb16 overexpression in xenograft mice inhibits tumor growth by inducing cell cycle arrest in the S phase through targeting WDHD1 transcription [3].

In type 2 diabetic mice, atrial-specific knockdown of Zbtb16 reduces the incidence and duration of atrial fibrillation by interrupting the Zbtb16-Txnip-Trx2 signaling pathway that induces excess reactive oxygen species release [4].

In conclusion, Zbtb16 is a key transcription factor with functions in osteogenesis, cancer development, and cardiac arrhythmia in the context of diabetes. Mouse models of Zbtb16 knockout or overexpression have provided valuable insights into its role in these disease-related biological processes, which may potentially lead to new therapeutic strategies.