| First Author | Rogers JH | Year | 2001 |
| Journal | J Mol Cell Cardiol | Volume | 33 |
| Issue | 2 | Pages | 209-18 |
| PubMed ID | 11162127 | Mgi Jnum | J:127759 |
| Mgi Id | MGI:3764782 | Doi | 10.1006/jmcc.2000.1307 |
| Citation | Rogers JH, et al. (2001) RGS4 reduces contractile dysfunction and hypertrophic gene induction in Galpha q overexpressing mice. J Mol Cell Cardiol 33(2):209-18 |
| abstractText | The intrinsic GTPase activity of Galpha q is low, and RGS proteins which activate GTPase are expressed in the heart; however, their functional relevance in vivo is unknown. Transgenic mice with cardiac-specific overexpression of Galpha q in myocardium exhibit cardiac hypertrophy, enhanced PKC xi membrane translocation, embryonic gene expression, and depressed cardiac contractility. We recently reported that transgenic mice with cardiac-specific expression of RGS4, a Galpha q and Galpha i GTPase activator, exhibit decreased left ventricular hypertrophy and ANF induction in response to pressure overload. To test the hypothesis that RGS4 can act as a Galpha q-specific GTPase activating protein (GAP) in the in vivo heart, dual transgenic Galpha q-40xRGS4 mice were generated to determine if RGS4 co-expression would ameliorate the Galpha q-40 phenotype. At age 4 weeks, percent fractional shortening was normalized in dual transgenic mice as was left ventricular internal dimension and posterior and septal wall thicknesses. PKC xi membrane translocation and ANF and alpha -skeletal actin mRNA levels were also normalized. Compound transgenic mice eventually developed depressed cardiac contractility that was evident by 9 weeks of age. These studies establish for the first time a role for RGS4 as a GAP for Galpha q in the in vivo heart, and demonstrate that its regulated expression can have pathophysiologic consequences. |
