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New mouse model for testing cancer drugs
Date:7/19/2011

sion of Plk1-specific RNA and, in turn, the silencing of the gene is only induced by the antibiotic Doxycycline. The mice are therefore able to mature and the relevant gene is not knocked down using Doxycycline until the mice have reached adult age.

The working group supervised by Prof. Strebhardt in cooperation with Bayer Schering Pharma AG and Taconic Artemis GmbH developed the mouse model (Plk1 iKD animals). The mice were subsequently phenotypically characterized. This was done together with the Helmholtz Center in Munich, Munich's two universities as well as the universities of Gieen and Hamburg. "Surprisingly, despite the efficient knock-down of Plk1 in various tissues of the mouse following administration of Doxycycline over a six-week period, no major structural or functional anomalies were identified," reported Strebhardt. "This observation is diametrically opposed to the role of Plk1 in cancer cells of varying origins which, following the inhibition of Plk1, quickly cease dividing and go into apoptosis." In order to further verify the surprising findings in the Plk1 iKD animals, the researchers examined various primary cells in culture under controlled conditions. Just as previously in the animal experiment, Plk1 expression was inhibited through RNA interference and analyzed. In this system, too, the results of the animal experiments were confirmed: In contrast to tumor cells, healthy cells are only dependent on Plk1 expression to a minimal degree. As such, healthy cells are virtually undamaged if the Plk1 gene is silenced while the cancer cells are combated.

"Inducible RNAi-based mouse models represent an attractive way of reversibly con-trolling gene expression in order to study the targeted inactivation of genes. Our work is a feasibility study which considers whether inducible RNAi-based mouse models are suitable for predicting the toxicity of targeted cancer drugs," explained Klaus Strebhardt. "The similar results of the Plk1 knockdow
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Contact: Prof. Klaus Strebhardt
Strebhardt@em.uni-frankfurt.de
49-696-301-6894
Goethe University Frankfurt
Source:Eurekalert

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