Cre/lox-assisted non-invasive in vivo tracking of specific cell populations by positron emission tomography

Martin Thunemann, Barbara F. Schörg, Susanne Feil, Yun Lin, Jakob Voelkl, Matthias Golla, Angelos Vachaviolos, Ursula Kohlhofer, Leticia Quintanilla-Martinez, Marcus Olbrich, Walter Ehrlichmann, Gerald Reischl, Christoph M. Griessinger, Harald F. Langer, Meinrad Gawaz, Florian Lang, Michael Schäfers, Manfred Kneilling, Bernd J. Pichler and Robert Feil ()
Additional contact information
Martin Thunemann: University of Tübingen
Barbara F. Schörg: University of Tübingen
Susanne Feil: University of Tübingen
Yun Lin: University of Tübingen
Jakob Voelkl: University of Tübingen
Matthias Golla: University of Tübingen
Angelos Vachaviolos: University of Tübingen
Ursula Kohlhofer: University of Tübingen, and Comprehensive Cancer Center, University Hospital
Leticia Quintanilla-Martinez: University of Tübingen, and Comprehensive Cancer Center, University Hospital
Marcus Olbrich: University of Tübingen
Walter Ehrlichmann: University of Tübingen
Gerald Reischl: University of Tübingen
Christoph M. Griessinger: University of Tübingen
Harald F. Langer: University of Tübingen
Meinrad Gawaz: University of Tübingen
Florian Lang: University of Tübingen
Michael Schäfers: University of Münster
Manfred Kneilling: University of Tübingen
Bernd J. Pichler: University of Tübingen
Robert Feil: University of Tübingen

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Many pathophysiological processes are associated with proliferation, migration or death of distinct cell populations. Monitoring specific cell types and their progeny in a non-invasive, longitudinal and quantitative manner is still challenging. Here we show a novel cell-tracking system that combines Cre/lox-assisted cell fate mapping with a thymidine kinase (sr39tk) reporter gene for cell detection by positron emission tomography (PET). We generate Rosa26-mT/sr39tk PET reporter mice and induce sr39tk expression in platelets, T lymphocytes or cardiomyocytes. As proof of concept, we demonstrate that our mouse model permits longitudinal PET imaging and quantification of T-cell homing during inflammation and cardiomyocyte viability after myocardial infarction. Moreover, Rosa26-mT/sr39tk mice are useful for whole-body characterization of transgenic Cre mice and to detect previously unknown Cre activity. We anticipate that the Cre-switchable PET reporter mice will be broadly applicable for non-invasive long-term tracking of selected cell populations in vivo.

Date: 2017
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DOI: 10.1038/s41467-017-00482-y

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