Non-invasive imaging of gene expression and protein secretion dynamics in living mice

Nourse, J.; Tokalov, S.; Khan, E.; Khokhar, S.; Schott, L. K.; Hinz, L.; Eder, L.; Arnold-Schild, D.; Probst, H. C.; Danckwardt, S.

doi:10.1101/2021.07.08.451623

bioRxiv · 10.1101/2021.07.08.451623

Non-invasive imaging of gene expression and protein secretion dynamics in living mice

Nourse, J.·Tokalov, S.·Khan, E.·Khokhar, S.·Schott, L. K.·Hinz, L.·Eder, L.·Arnold-Schild, D.·Probst, H. C.·Danckwardt, S.

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Abstract

The topology of gene expression and protein localization is a crucial characteristic of life, where the spatiotemporal dynamic of secretory proteins instruct higher order organization, including the orchestration of developmental and adaptive programs. However tools to non-invasively interrogate the fate of secretory proteins in vivo are scarce. Here we introduce a genetic tagging strategy for in vivo imaging of the secretion and expression dynamics of secretory proteins in living animals. Applying this to a prototypical liver-derived secretory protein, we demonstrate that this approach, combined with optical in-vivo imaging, uncovers extrahepatic prothrombin expression in multiple novel anatomical sites (including testes, placenta, brain, kidney, heart and lymphatic system) and in emerging tumors, resulting in significant amounts of tumor-derived prothrombin in the blood with procoagulant properties. Syngeneic cell lines from this mouse model enable unravelling regulatory mechanisms in high resolution, and in a scalable format ex vivo. Beyond discovering new functions of proteins in a targeted manner, this model allows identifying rheostats in the cross-talk between gene expression and availability of a secretory protein. It is also a valuable resource for uncovering novel (tissue-specific) therapeutic vulnerabilities.

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Nourse, J., Tokalov, S., Khan, E., Khokhar, S., Schott, L. K., Hinz, L., Eder, L., Arnold-Schild, D., Probst, H. C., Danckwardt, S.. 2021-07-09. Non-invasive imaging of gene expression and protein secretion dynamics in living mice. https://doi.org/10.1101/2021.07.08.451623

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