Optimization of spatiotemporal gene inactivation in mouse heart by oral application of tamoxifen citrate

Inducible and tissue‐specific gene inactivation in mice has become a powerful tool to bypass embryonic and postnatal lethality of knockout mice. The most frequently used inducible system is based on Cre recombinase fused to either one or two mutated estrogen receptor ligand binding domains, thus ren...

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Published in:Genesis (New York, N.Y. : 2000) N.Y. : 2000), 2007-01, Vol.45 (1), p.11-16
Main Authors: Kiermayer, Claudia, Conrad, Marcus, Schneider, Manuela, Schmidt, Jörg, Brielmeier, Markus
Format: Article
Language:English
Subjects:
Animals
Cre recombinase
inducible gene expression
Integrases - genetics
MerCreMer
Mice
Mice, Transgenic
mitochondrial thioredoxin reductase
Myocardium - enzymology
oral administration
Tamoxifen - administration & dosage
Tamoxifen - adverse effects
Tamoxifen - pharmacology
tamoxifen citrate salt
Thioredoxin Reductase 2
Thioredoxin-Disulfide Reductase - biosynthesis
Thioredoxin-Disulfide Reductase - genetics
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Summary:Inducible and tissue‐specific gene inactivation in mice has become a powerful tool to bypass embryonic and postnatal lethality of knockout mice. The most frequently used inducible system is based on Cre recombinase fused to either one or two mutated estrogen receptor ligand binding domains, thus rendering Cre function tamoxifen‐dependent. To achieve Cre‐mediated inactivation of a given gene, 4‐OH tamoxifen (4‐OHT) dissolved either in alcohol and/or oil is usually administered by repeated intraperitoneal (i.p.) injections. Since this procedure imposes considerable stress on mice, we compared the effect of tamoxifen citrate, mixed into a standard mouse diet at different concentrations, with that of i.p. administration of 4‐OHT on Cre‐mediated, heart‐specific inactivation of thioredoxin reductase 2. Here we show that tamoxifen citrate in the chow was equally effective as 4‐OHT given i.p. Oral tamoxifen administration is thus a convenient and cost‐saving way for gene induction, and, most importantly, it reduces stress and avoids adverse effects in mice. genesis 45:11–16, 2007. © 2007 Wiley‐Liss, Inc.
ISSN:1526-954X
1526-968X
DOI:10.1002/dvg.20244