RGD Reference Report - Cardiac hypertrophy in transgenic rats expressing a dominant-negative mutant of the natriuretic peptide receptor B. - Rat Genome Database

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Cardiac hypertrophy in transgenic rats expressing a dominant-negative mutant of the natriuretic peptide receptor B.

Authors: Langenickel, TH  Buttgereit, J  Pagel-Langenickel, I  Lindner, M  Monti, J  Beuerlein, K  Al-Saadi, N  Plehm, R  Popova, E  Tank, J  Dietz, R  Willenbrock, R  Bader, M 
Citation: Langenickel TH, etal., Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4735-40. Epub 2006 Mar 14.
RGD ID: 1601488
Pubmed: PMID:16537417   (View Abstract at PubMed)
PMCID: PMC1450239   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0510019103   (Journal Full-text)

Natriuretic peptides (NP) mediate their effects by activating membrane-bound guanylyl cyclase-coupled receptors A (NPR-A) or B (NPR-B). Whereas the pathophysiological role of NPR-A has been widely studied, only limited knowledge on the cardiovascular function of NPR-B is available. In vitro studies suggest antiproliferative and antihypertrophic actions of the NPR-B ligand C-type NP (CNP). Because of the lack of a specific pharmacological inhibitor, these effects could not clearly be attributed to impaired NPR-B signaling. Recently, gene deletion revealed a predominant role of NPR-B in endochondral ossification and development of female reproductive organs. However, morphological abnormalities and premature death of NPR-B-deficient mice preclude detailed cardiovascular phenotyping. In the present study, a dominant-negative mutant (NPR-BDeltaKC) was used to characterize CNP-dependent NPR-B signaling in vitro and in transgenic rats. Here we demonstrate that reduced CNP- but not atrial NP-dependent cGMP response attenuates antihypertrophic potency of CNP in vitro. In transgenic rats, NPR-BDeltaKC expression selectively reduced NPR-B but not NPR-A signaling. NPR-BDeltaKC transgenic rats display progressive, blood pressure-independent cardiac hypertrophy and elevated heart rate. The hypertrophic phenotype is further enhanced in chronic volume overload-induced congestive heart failure. Thus, this study provides evidence linking NPR-B signaling to the control of cardiac growth.

Gene Ontology Annotations    

Molecular Function

Molecular Pathway Annotations    
Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Nppc  (natriuretic peptide C)
Npr2  (natriuretic peptide receptor 2)

Genes (Mus musculus)
Nppc  (natriuretic peptide type C)
Npr2  (natriuretic peptide receptor 2)

Genes (Homo sapiens)
NPPC  (natriuretic peptide C)
NPR2  (natriuretic peptide receptor 2)

Additional Information