title: Cardiovascular response to beta-adrenergic blockade or activation in 23 inbred mouse strains.
abstract: We report the characterisation of 27 cardiovascular-related traits in 23 inbred mouse strains. Mice were phenotyped either in response to chronic administration of a single dose of the beta-adrenergic receptor blocker atenolol or under a low and a high dose of the beta-agonist isoproterenol and compared to baseline condition. The robustness of our data is supported by high trait heritabilities (typically H(2)>0.7) and significant correlations of trait values measured in baseline condition with independent multistrain datasets of the Mouse Phenome Database. We then focused on the drug-, dose-, and strain-specific responses to beta-stimulation and beta-blockade of a selection of traits including heart rate, systolic blood pressure, cardiac weight indices, ECG parameters and body weight. Because of the wealth of data accumulated, we applied integrative analyses such as comprehensive bi-clustering to investigate the structure of the response across the different phenotypes, strains and experimental conditions. Information extracted from these analyses is discussed in terms of novelty and biological implications. For example, we observe that traits related to ventricular weight in most strains respond only to the high dose of isoproterenol, while heart rate and atrial weight are already affected by the low dose. Finally, we observe little concordance between strain similarity based on the phenotypes and genotypic relatedness computed from genomic SNP profiles. This indicates that cardiovascular phenotypes are unlikely to segregate according to global phylogeny, but rather be governed by smaller, local differences in the genetic architecture of the various strains.
authors: Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors: Corinne
authors: C
authors: Berthonneche
authors: Bastian
authors: B
authors: Peter
authors: Fanny
authors: F
authors: Schüpfer
authors: Pamela
authors: P
authors: Hayoz
authors: Zoltán
authors: Z
authors: Kutalik
authors: Hugues
authors: H
authors: Abriel
authors: Thierry
authors: T
authors: Pedrazzini
authors: Jacques S
authors: JS
authors: Beckmann
authors: Sven
authors: S
authors: Bergmann
authors: Fabienne
authors: F
authors: Maurer
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D010641:Phenotype
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D007545:Isoproterenol