Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-10

AUTHORS

Kornélia Szebényi, András Füredi, Orsolya Kolacsek, Enikő Pergel, Zsuzsanna Bősze, Balázs Bender, Péter Vajdovich, József Tóvári, László Homolya, Gergely Szakács, László Héja, Ágnes Enyedi, Balázs Sarkadi, Ágota Apáti, Tamás I. Orbán

ABSTRACT

In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG-GCaMP2 expressing construct, and animals with one transgene copy were pre-selected by measuring fluorescence in blood cells. A homozygous rat strain was generated with high sensor protein expression in the heart, kidney, liver, and blood cells. No pathological alterations were found in these animals, and fluorescence measurements in cardiac tissue slices and primary cultures demonstrated the applicability of this system for studying calcium signaling. We show here that the GCaMP2 expressing rat cardiomyocytes allow the prediction of cardiotoxic drug side-effects, and provide evidence for the role of Na(+)/Ca(2+) exchanger and its beneficial pharmacological modulation in cardiac reperfusion. Our data indicate that drug-induced alterations and pathological processes can be followed by using this rat model, suggesting that transgenic rats expressing a calcium-sensitive protein provide a valuable system for pharmacological and toxicological studies. More... »

PAGES

12645

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep12645

DOI

http://dx.doi.org/10.1038/srep12645

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1003561499

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26234466


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