Circulation Research. 2001;89:20-25
Published online before print June 21, 2001, doi: 10.1161/hh1301.092687
Published online before print June 21, 2001, doi: 10.1161/hh1301.092687
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© 2001 American Heart Association, Inc.
Molecular Medicine |
Temporally Regulated and Tissue-Specific Gene Manipulations in the Adult and Embryonic Heart Using a Tamoxifen-Inducible Cre Protein
From the Department of Pediatrics (D.S.S., S.A.W., T.R.K., K.M.T., J.D.M.), University of Cincinnati, Children’s Hospital Medical Center, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio, and Amgen Institute (M.N., M.A.C., J.M.P.), Toronto, Ontario, Canada.
Correspondence to Jeffery D. Molkentin, Department of Pediatrics, Children’s Hospital Medical Center, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, Cincinnati, OH 45229-3039. E-mail jeff.molkentin{at}chmcc.org
Abstract
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 
-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.
Key Words: cardiac • cre recombinase • genetics • inducible gene expression • embryo
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