Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown.

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 e...

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Autores principales:	Katarina Kotnik, Elena Popova, Mihail Todiras, Marcelo A Mori, Natalia Alenina, Jost Seibler, Michael Bader
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/788b7714876544118cfc35c405df8dfb
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spelling	oai:doaj.org-article:788b7714876544118cfc35c405df8dfb2021-11-25T06:16:22ZInducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown.1932-620310.1371/journal.pone.0005124https://doaj.org/article/788b7714876544118cfc35c405df8dfb2009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19340286/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Katarina KotnikElena PopovaMihail TodirasMarcelo A MoriNatalia AleninaJost SeiblerMichael BaderPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 4, p e5124 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katarina Kotnik Elena Popova Mihail Todiras Marcelo A Mori Natalia Alenina Jost Seibler Michael Bader Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown.
description	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.
format	article
author	Katarina Kotnik Elena Popova Mihail Todiras Marcelo A Mori Natalia Alenina Jost Seibler Michael Bader
author_facet	Katarina Kotnik Elena Popova Mihail Todiras Marcelo A Mori Natalia Alenina Jost Seibler Michael Bader
author_sort	Katarina Kotnik
title	Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown.
title_short	Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown.
title_full	Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown.
title_fullStr	Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown.
title_full_unstemmed	Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown.
title_sort	inducible transgenic rat model for diabetes mellitus based on shrna-mediated gene knockdown.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/788b7714876544118cfc35c405df8dfb
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Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown.

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