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Generation and characterization of a novel, cardiac‐specific, inducible RGS2 transgenic mouse model to modulate Gq‐mediated cardiac hypertrophy
Author(s) -
Park Cindy,
Zhu Ming,
Chaves Leonard,
Zhang Peng,
King Michelle,
Mende Ulrike
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb46
Subject(s) - rgs2 , pressure overload , transgene , muscle hypertrophy , genetically modified mouse , medicine , heterotrimeric g protein , g protein , gq alpha subunit , biology , in vivo , endocrinology , microbiology and biotechnology , signal transduction , chemistry , gtpase activating protein , biochemistry , cardiac hypertrophy , gene , genetics
Receptor signaling via heterotrimeric G q proteins leads to hypertrophy, which is a risk factor for heart failure. Among R egulators of G ‐protein S ignaling (RGS), only RGS2 selectively inhibits G q signaling and hypertrophy in cardiomyocytes in vitro . Our objective was to generate a mouse model that is suitable to test the hypothesis that RGS2 can modulate hypertrophy development and reversal in vivo. Using a doxycycline (Dox)‐responsive α myosin heavy chain promoter, we generated transgenic mice with cardiac‐specific, conditional RGS2 expression (TG) and established a Dox regimen that prevents RGS2 expression during development and ensures re‐expression by adulthood. Transgenic RGS2 was restricted to the myocardium, localized to both the particulate and cytosolic fraction, and dose‐dependently regulated by Dox in two independent lines. RGS2 expression did not alter heart weight, morphology and function under baseline conditions. Importantly, G q ‐mediated phospholipase Cβ activation was diminished in RGS2‐expressing ventricles. Our data indicate proper expression, regulation and function of transgenic RGS2 with no compensatory changes in other RGS proteins. Thus, this novel transgenic mouse model can now be used to determine the effect of RGS2 on G q ‐mediated pressure overload hypertrophy in vivo, using echocardiography and hemodynamic measurements. Supported by NIH grant HL80127.