Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse

Aberrant AKT activation occurs in a number of cancers, metabolic syndrome, and immune disorders, making it an important target for the treatment of many diseases. To monitor spatial and temporal AKT activity in a live setting, we generated an Akt-FRET biosensor mouse that allows longitudinal assessment of AKT activity using intravital imaging in conjunction with image stabilization and optical window technology. We demonstrate the sensitivity of the Akt-FRET biosensor mouse using various cancer models and verify its suitability to monitor response to drug targeting in spheroid and organotypic models. We also show that the dynamics of AKT acti-vation can be monitored in real time in diverse tissues, including in individual islets of the pancreas, in the brown and white adipose tissue, and in the skeletal muscle. Thus, the Akt-FRET biosensor mouse provides an important tool to study AKT dynamics in live tissue contexts and has broad preclinical applications.

Automated summary

Aberrant AKT activation is implicated in various diseases, and therefore targeting AKT has become a significant approach for disease treatment. In this study, we developed an Akt-FRET biosensor mouse that enables the monitoring of AKT activity in live tissues. We demonstrated the sensitivity of this biosensor mouse in different cancer models and showed its suitability for evaluating drug response. Additionally, we observed real-time dynamics of AKT activation in diverse tissues, indicating the broad preclinical applications of this biosensor mouse for studying AKT dynamics in vivo.