1. Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse
- Author
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James R. W. Conway, Sean C. Warren, Young-Kyung Lee, Andrew T. McCulloch, Astrid Magenau, Victoria Lee, Xanthe L. Metcalf, Janett Stoehr, Katharina Haigh, Lea Abdulkhalek, Cristian S. Guaman, Daniel A. Reed, Kendelle J. Murphy, Brooke A. Pereira, Pauline Mélénec, Cecilia Chambers, Sharissa L. Latham, Helen Lenthall, Elissa K. Deenick, Yuanqing Ma, Tri Phan, Elgene Lim, Anthony M. Joshua, Stacey Walters, Shane T. Grey, Yan-Chuan Shi, Lei Zhang, Herbert Herzog, David R. Croucher, Andy Philp, Colinda L.G.J. Scheele, David Herrmann, Owen J. Sansom, Jennifer P. Morton, Antonella Papa, Jody J. Haigh, Max Nobis, and Paul Timpson
- Subjects
Mice ,Multidisciplinary ,Fluorescence Resonance Energy Transfer ,Animals ,Biosensing Techniques ,Proto-Oncogene Proteins c-akt - Abstract
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 activation 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. ispartof: SCIENCE ADVANCES vol:9 issue:17 ispartof: location:United States status: published
- Published
- 2023
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