Skip to main content
Article thumbnail
Location of Repository

Inducible Transgenic Rat Model for Diabetes Mellitus Based on shRNA-Mediated Gene Knockdown

By Katarina Kotnik, Elena Popova, Mihail Todiras, Marcelo A. Mori, Natalia Alenina, Jost Seibler and Michael Bader


The rat is an important animal model in biomedical research, but gene targeting technology is not established for this species. Therefore, we aimed to produce transgenic knockdown rats using shRNA technology and pronuclear microinjection. To this purpose, we employed a tetracycline-inducible shRNA expression system targeting the insulin receptor (IR). Doxycycline (DOX) treatment of the resulting transgenic rats led to a dose-dependent and reversible increase in blood glucose caused by ubiquitous inhibition of IR expression and signalling. We could neither detect an interferon response nor disturbances in microRNA processing after DOX treatment excluding toxic effects of shRNA expression. Low dose DOX treatment induced a chronic state of diabetes mellitus. In conclusion, we have developed a technology which allows the specific, inducible, and reversible suppression of any gene of interest in the rat. Our first transgenic rat line generated with this method represents an inducible model for diabetes mellitus

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    1. (2006). A transgenic approach for RNA interferencebased genetic screening in mice.
    2. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
    3. (2005). Animal models of diabetes mellitus.
    4. (2008). Capture of authentic embryonic stem cells from rat blastocysts.
    5. (2005). Conditional knockdown of Fgfr2 in mice using Cre-LoxP induced RNA interference.
    6. (2004). Crelox-regulated conditional RNA interference from transgenes.
    7. (2005). Development and application of rodent models for type 2 diabetes.
    8. (2005). DNA constructs designed to produce short hairpin, interfering RNAs in transgenic mice sometimes show early lethality and an interferon response.
    9. (1996). Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice.
    10. (1991). Efficient selection for high-expression transfectants with a novel eukaryotic vector.
    11. (2008). Endothelial dysfunction and elevated blood pressure in Mas gene-deleted mice.
    12. (2006). Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways.
    13. (2008). Germline competent embryonic stem cells derived from rat blastocysts.
    14. (2003). Germline transmission of RNAi in mice.
    15. (2006). Heritable and stable gene knockdown in rats.
    16. (2008). Inducible and reversible gene silencing by stable integration of an shRNA-encoding lentivirus in transgenic rats.
    17. (2003). Inducible shRNA expression for application in a prostate cancer mouse model.
    18. (2005). Induction and analysis of cardiac hypertrophy in transgenic animal models.
    19. (2003). Induction of an interferon response by RNAi vectors in mammalian cells.
    20. (2006). Induction of the interferon response by siRNA is cell type- and duplex lengthdependent.
    21. (2005). Krivokharchenko A
    22. (2006). Pol II-expressed shRNA knocks down Sod2 gene expression and causes phenotypes of the gene knockout in mice.
    23. (2005). Probing tumor phenotypes using stable and regulated synthetic microRNA precursors.
    24. (2008). Progress and prospects in rat genetics: a community view.
    25. (2003). Rat models of the metabolic syndrome.
    26. (2006). Reproducible and inducible knockdown of gene expression in mice.
    27. (2007). Reversible gene knockdown in mice using a tight, inducible shRNA expression system.
    28. (2004). Short-term cytotoxic effects and long-term instability of RNAi delivered using lentiviral vectors.
    29. (2005). Single copy shRNA configuration for ubiquitous gene knockdown in mice.
    30. (2002). Studying gene function in eukaryotes by conditional gene inactivation.
    31. (1994). Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter.
    32. (2000). Tetracycline-regulated gene expression in the brain.
    33. (2007). Tissue-specific and reversible RNA interference in transgenic mice.
    34. (1988). Tn10-encoded tet repressor can regulate an operatorcontaining plant promoter.
    35. (2005). Transgenic small interfering RNA halts amyotrophic lateral sclerosis in a mouse model.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.