Depot formation of doxycycline impairs Tet-regulated gene expression in vivo Journal Article

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Authors: Anders, K.; Buschow, C.; Charo, J.; Blankenstein, T.
Article Title: Depot formation of doxycycline impairs Tet-regulated gene expression in vivo
Abstract: The tetracycline (Tet) system is widely used for regulation of gene expression in vitro and in vivo. We constructed C57BL/6 transgenic mice (rtTA-CM2) with strong and ubiquitous reverse transactivator (rtTA2(S)-M2) gene expression. rtTA-CM2 mice were crossed to Tet-responsive reporter mice (LC-1) conditionally expressing the firefly luciferase (FLuc) gene under control of a Tet-responsive element, which allowed sensitive quantification of the transactivator activity by bioluminescent imaging. Following doxycycline (dox) application, up to 10(5)-fold increase in BL signal was measured. rtTA activity was inducible in most analyzed organs. After dox withdrawal the BL signal decreased significantly but did not disappear completely, most likely due to a dox depot formation in vivo. The residual dox was sufficient to partly down-regulate a Tet-off controlled oncogene in a tumor transplantation experiment, resulting in reduced tumor growth. rtTA-CM2 mice may be a useful tool to analyze the function of genes in various organs but also reveal that down-regulation of gene expression is not complete.
Journal Title: Transgenic research
Volume: 21
Issue: 5
ISSN: 1573-9368; 0962-8819
Publisher: Unknown  
Journal Place: Netherlands
Date Published: 2012
Start Page: 1099
End Page: 1107
Language: eng
DOI/URL:

10.1007/s11248-011-9580-0

10.1007/s11248-011-9580-0
Notes: JID: 9209120; 0 (Antigens, Polyomavirus Transforming); 0 (Antineoplastic Agents); 0 (Oncogene Proteins, Fusion); 0 (Trans-Activators); 564-25-0 (Doxycycline); EC 1.13.12.- (Luciferases); 2011/09/21 [received]; 2011/11/30 [accepted]; 2011/12/14 [aheadofprint]; ppublish
LUC Authors
  1. Jehad Charo
    1 Charo
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