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Cardiovascular response to beta-adrenergic blockade or activation in 23 inbred mouse strains.

Berthonneche C, Peter B, Schüpfer F, Hayoz P, Kutalik Z, Abriel H, Pedrazzini T, Beckmann JS, Bergmann S, Maurer F - PLoS ONE (2009)

Bottom Line: 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.Information extracted from these analyses is discussed in terms of novelty and biological implications.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.

View Article: PubMed Central - PubMed

Affiliation: Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

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.

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Means and standard deviations of ten selected phenotypes in 23 inbred mouse strains.White bars: ctr; blue bars: ate; orange bars: iso1; red bars: iso10. Strains are ranked by increasing HR (TC) means of ctr mice. See Table 1 for abbreviations.
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pone-0006610-g002: Means and standard deviations of ten selected phenotypes in 23 inbred mouse strains.White bars: ctr; blue bars: ate; orange bars: iso1; red bars: iso10. Strains are ranked by increasing HR (TC) means of ctr mice. See Table 1 for abbreviations.

Mentions: In this study, hereafter abbreviated CV-PGX (for “cardio-vascular pharmaco-genomics”), we have characterised 23 inbred mouse strains for 27 cardiovascular and related phenotypes such as systolic blood pressure (SBP), heart rate (HR), electrocardiogram (ECG) parameters and cardiac weight indices, either under baseline condition (ctr) or in response to chronic administration of isoproterenol at 1 (iso1) or 10 (iso10) mg/kg per day or atenolol at 10 mg/kg per day (ate), as described in Materials and Methods and in Figure 1. Traits are listed in Table 1 and mean values and standard deviations of ten selected phenotypes across all strains and drug conditions are presented as bar graphs in Figure 2 (see Supplement S1 for all traits). One-way Analyses Of Variance (ANOVA) showed high reproducibility for all phenotypes measured under ctr or any given treatment. In particular, variances were significantly smaller within than between strains, indicating that all phenotypic responses are highly heritable (typically 0.7<H2<1; Supplement S1).


Cardiovascular response to beta-adrenergic blockade or activation in 23 inbred mouse strains.

Berthonneche C, Peter B, Schüpfer F, Hayoz P, Kutalik Z, Abriel H, Pedrazzini T, Beckmann JS, Bergmann S, Maurer F - PLoS ONE (2009)

Means and standard deviations of ten selected phenotypes in 23 inbred mouse strains.White bars: ctr; blue bars: ate; orange bars: iso1; red bars: iso10. Strains are ranked by increasing HR (TC) means of ctr mice. See Table 1 for abbreviations.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2722085&req=5

pone-0006610-g002: Means and standard deviations of ten selected phenotypes in 23 inbred mouse strains.White bars: ctr; blue bars: ate; orange bars: iso1; red bars: iso10. Strains are ranked by increasing HR (TC) means of ctr mice. See Table 1 for abbreviations.
Mentions: In this study, hereafter abbreviated CV-PGX (for “cardio-vascular pharmaco-genomics”), we have characterised 23 inbred mouse strains for 27 cardiovascular and related phenotypes such as systolic blood pressure (SBP), heart rate (HR), electrocardiogram (ECG) parameters and cardiac weight indices, either under baseline condition (ctr) or in response to chronic administration of isoproterenol at 1 (iso1) or 10 (iso10) mg/kg per day or atenolol at 10 mg/kg per day (ate), as described in Materials and Methods and in Figure 1. Traits are listed in Table 1 and mean values and standard deviations of ten selected phenotypes across all strains and drug conditions are presented as bar graphs in Figure 2 (see Supplement S1 for all traits). One-way Analyses Of Variance (ANOVA) showed high reproducibility for all phenotypes measured under ctr or any given treatment. In particular, variances were significantly smaller within than between strains, indicating that all phenotypic responses are highly heritable (typically 0.7<H2<1; Supplement S1).

Bottom Line: 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.Information extracted from these analyses is discussed in terms of novelty and biological implications.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.

View Article: PubMed Central - PubMed

Affiliation: Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

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.

Show MeSH
Related in: MedlinePlus