Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline induction
Identifieur interne : 000781 ( Main/Exploration ); précédent : 000780; suivant : 000782Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline induction
Auteurs : Gusztav Belteki [Canada] ; Jody Haigh [Canada] ; Nikolett Kabacs [Canada] ; Katharina Haigh [Canada] ; Karen Sison [Canada] ; Frank Costantini [États-Unis] ; Jeff Whitsett [États-Unis] ; Susan E. Quaggin [Canada] ; Andras Nagy [Canada]Source :
- Nucleic Acids Research [ 0305-1048 ] ; 2005.
Abstract
Here we describe a triple transgenic mouse system, which combines the tissue specificity of any Cre-transgenic line with the inducibility of the reverse tetracycline transactivator (rtTA)/tetracycline-responsive element (tet-O)-driven transgenes. To ensure reliable rtTA expression in a broad range of cell types, we have targeted the rtTA transgene into the ROSA26 locus. The rtTA expression, however, is conditional to a Cre recombinase-mediated excision of a STOP region from the ROSA26 locus. We demonstrate the utility of this technology through the inducible expression of the vascular endothelial growth factor (VEGF-A) during embryonic development and postnatally in adult mice. Our results of adult induction recapitulate several different hepatic and immune cell pathological phenotypes associated with increased systemic VEGF-A protein levels. This system will be useful for studying genes in which temporal control of expression is necessary for the discovery of the full spectrum of functions. The presented approach abrogates the need to generate tissue-specific rtTA transgenes for tissues where well-characterized Cre lines already exist.
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DOI: 10.1093/nar/gni051
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Acids Res.</title><idno type="ISSN">0305-1048</idno><idno type="eISSN">1362-4962</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2005">2005</date><biblScope unit="volume">33</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="e51">e51</biblScope><biblScope unit="page" to="e51">e51</biblScope></imprint><idno type="ISSN">0305-1048</idno></series><idno type="istex">575A726A7C2FF59BC3829CD72A1E03EE4B5A9F41</idno><idno type="DOI">10.1093/nar/gni051</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0305-1048</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Here we describe a triple transgenic mouse system, which combines the tissue specificity of any Cre-transgenic line with the inducibility of the reverse tetracycline transactivator (rtTA)/tetracycline-responsive element (tet-O)-driven transgenes. To ensure reliable rtTA expression in a broad range of cell types, we have targeted the rtTA transgene into the ROSA26 locus. The rtTA expression, however, is conditional to a Cre recombinase-mediated excision of a STOP region from the ROSA26 locus. We demonstrate the utility of this technology through the inducible expression of the vascular endothelial growth factor (VEGF-A) during embryonic development and postnatally in adult mice. Our results of adult induction recapitulate several different hepatic and immune cell pathological phenotypes associated with increased systemic VEGF-A protein levels. This system will be useful for studying genes in which temporal control of expression is necessary for the discovery of the full spectrum of functions. The presented approach abrogates the need to generate tissue-specific rtTA transgenes for tissues where well-characterized Cre lines already exist.</div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Ohio</li><li>État de New York</li></region></list><tree><country name="Canada"><noRegion><name sortKey="Belteki, Gusztav" sort="Belteki, Gusztav" uniqKey="Belteki G" first="Gusztav" last="Belteki">Gusztav Belteki</name></noRegion><name sortKey="Haigh, Jody" sort="Haigh, Jody" uniqKey="Haigh J" first="Jody" last="Haigh">Jody Haigh</name><name sortKey="Haigh, Katharina" sort="Haigh, Katharina" uniqKey="Haigh K" first="Katharina" last="Haigh">Katharina Haigh</name><name sortKey="Kabacs, Nikolett" sort="Kabacs, Nikolett" uniqKey="Kabacs N" first="Nikolett" last="Kabacs">Nikolett Kabacs</name><name sortKey="Nagy, Andras" sort="Nagy, Andras" uniqKey="Nagy A" first="Andras" last="Nagy">Andras Nagy</name><name sortKey="Nagy, Andras" sort="Nagy, Andras" uniqKey="Nagy A" first="Andras" last="Nagy">Andras Nagy</name><name sortKey="Nagy, Andras" sort="Nagy, Andras" uniqKey="Nagy A" first="Andras" last="Nagy">Andras Nagy</name><name sortKey="Nagy, Andras" sort="Nagy, Andras" uniqKey="Nagy A" first="Andras" last="Nagy">Andras Nagy</name><name sortKey="Quaggin, Susan E" sort="Quaggin, Susan E" uniqKey="Quaggin S" first="Susan E." last="Quaggin">Susan E. Quaggin</name><name sortKey="Quaggin, Susan E" sort="Quaggin, Susan E" uniqKey="Quaggin S" first="Susan E." last="Quaggin">Susan E. Quaggin</name><name sortKey="Sison, Karen" sort="Sison, Karen" uniqKey="Sison K" first="Karen" last="Sison">Karen Sison</name></country><country name="États-Unis"><region name="État de New York"><name sortKey="Costantini, Frank" sort="Costantini, Frank" uniqKey="Costantini F" first="Frank" last="Costantini">Frank Costantini</name></region><name sortKey="Whitsett, Jeff" sort="Whitsett, Jeff" uniqKey="Whitsett J" first="Jeff" last="Whitsett">Jeff Whitsett</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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