Abstract
The advent of conditional and tissue-specific recombination systems
in gene-targeted or transgenic mice has permitted an assessment of
single gene function in a temporally regulated and cell-specific
manner. Here we generated transgenic mice expressing a tamoxifen-inducible
Cre recombinase protein fused to two mutant estrogen-receptor ligand-binding
domains (MerCreMer) under the control of the alpha-myosin heavy chain
promoter. These transgenic mice were crossed with the ROSA26 lacZ-flox-targeted
mice to examine Cre recombinase activity and the fidelity of the
system. The data demonstrate essentially no Cre-mediated recombination
in the embryonic, neonatal, or adult heart in the absence of inducing
agent but >80\% recombination after only four tamoxifen injections.
Expression of the MerCreMer fusion protein within the adult heart
did not affect cardiac performance, cellular architecture, or expression
of hypertrophic marker genes, demonstrating that the transgene-encoded
protein is relatively innocuous. In summary, MerCreMer transgenic
mice represent a tool for temporally regulated inactivation of any
loxP-targeted gene within the developing and adult heart or for specifically
directing recombination and expression of a loxP-inactivated cardiac
transgene in the heart.
- 11440973
- animals,
- estrogen
- estrogen,
- expression
- fusion
- gene
- genetic,
- gov't,
- heart,
- integrases,
- kinetics,
- messenger,
- mice,
- modulators,
- myocardium,
- non-u.s.
- p.h.s.,
- proteins,
- receptor
- receptors,
- recombinant
- recombination,
- regulation,
- research
- rna,
- selective
- support,
- tamoxifen,
- transgenes,
- transgenic,
- u.s.
- viral
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