# Generation and characterization of a Cre-inducible ZNF768 overexpression mouse model

## TL;DR

Scientists created a mouse model to study the effects of overexpressing ZNF768, finding it doesn't cause cancer on its own.

## Contribution

A new Cre-inducible mouse model for conditional ZNF768 overexpression was generated and characterized.

## Key findings

- ZNF768 overexpression in mice did not lead to visible phenotypes or developmental issues.
- Forced ZNF768 expression did not promote tumor development in models of fibrosarcoma and lung adenocarcinoma.
- The generated mouse model allows conditional ZNF768 overexpression for future functional studies.

## Abstract

Zinc-finger protein 768 (ZNF768) is an emerging transcription factor regulating cell proliferation and senescence. Although the role of ZNF768 in regulating cell fate decision has been demonstrated in vitro, its importance in controlling physiological and pathophysiological processes in vivo is still unclear. Here, we report the generation of a transgenic mouse model allowing the conditional overexpression of ZNF768. This was achieved by inserting an inverted Znf768 coding sequence surrounded by heterologous Cre recognition sites in the Gt(ROSA)26Sor mouse locus (FLExZnf768). To study the impact linked to systemic overexpression of ZNF768, mice carrying the FLExZnf768 allele were crossed with CMV-Cre mice to produce a whole-body ZNF768 transgenic mouse (WB-ZNF768-Tg). As expected, WB-ZNF768-Tg mice showed higher ZNF768 levels in various tissues. These mice were born at the expected Mendelian ratio and did not display apparent phenotypes. Because ZNF768 levels are often overexpressed in cancer, we assessed tumor development in WB-ZNF768-Tg mice. However, ZNF768 overexpression was not sufficient to promote 3-methylcholantrene-induced fibrosarcoma and KRASG12D-induced lung adenocarcinoma in mice. Overall, we report the generation of a conditional mouse for ZNF768 overexpression and reveal that forcing ZNF768 expression is not sufficient to alter tumour development in mice.