Limits...
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.

Show MeSH

Related in: MedlinePlus

Patterns of phenotype and strain correlations under drug treatment.For each strain (rows) and combination (columns) of a phenotype and a treatment (ate, iso1, iso10) the significance (signed -log10 value of Wilcoxon ranksum test, as used in Figure 4) of the phenotypic response with respect to the ctr group is shown using a colour code. Rows and columns are clustered according to pattern similarity. The branches of the dendrograms illustrating the clusters are plotted with the same colour as long as the average linkage distance is less than 50% of the maximal distance. AC: ate vs ctr; I1C: iso1 vs ctr; I10C: iso10 vs ctr. See Table 1 for abbreviations. HR std: standard deviation of HR (TC) strain means; SBP std: standard deviation of SBP strain means.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2722085&req=5

pone-0006610-g006: Patterns of phenotype and strain correlations under drug treatment.For each strain (rows) and combination (columns) of a phenotype and a treatment (ate, iso1, iso10) the significance (signed -log10 value of Wilcoxon ranksum test, as used in Figure 4) of the phenotypic response with respect to the ctr group is shown using a colour code. Rows and columns are clustered according to pattern similarity. The branches of the dendrograms illustrating the clusters are plotted with the same colour as long as the average linkage distance is less than 50% of the maximal distance. AC: ate vs ctr; I1C: iso1 vs ctr; I10C: iso10 vs ctr. See Table 1 for abbreviations. HR std: standard deviation of HR (TC) strain means; SBP std: standard deviation of SBP strain means.

Mentions: Each drug treatment was assessed for its impact on the patterns of correlations across mean trait values or strains (see Suppl. Figures 5–7 in Supplement S1). The high correlations between HW, AW, VW and BWE were globally maintained also upon perturbations of the β-adrenergic system but were slightly reduced under iso10 as compared to ctr mice (i.e. 0.4<r<0.8; compare Suppl. Figures 6A and 6D in Supplement S1). High similarity of HW and VW with Pdur was still detected under β-stimulation (i.e. 0.5<r<0.8) but it was significantly reduced under ate (r = 0.19, p = 0.38). Again and irrespective of the drug condition, no significant correlation could be identified between HR and SBP, between HR and VWI or AWI, and between SBP and AWI or VWI.


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)

Patterns of phenotype and strain correlations under drug treatment.For each strain (rows) and combination (columns) of a phenotype and a treatment (ate, iso1, iso10) the significance (signed -log10 value of Wilcoxon ranksum test, as used in Figure 4) of the phenotypic response with respect to the ctr group is shown using a colour code. Rows and columns are clustered according to pattern similarity. The branches of the dendrograms illustrating the clusters are plotted with the same colour as long as the average linkage distance is less than 50% of the maximal distance. AC: ate vs ctr; I1C: iso1 vs ctr; I10C: iso10 vs ctr. See Table 1 for abbreviations. HR std: standard deviation of HR (TC) strain means; SBP std: standard deviation of SBP strain means.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006610-g006: Patterns of phenotype and strain correlations under drug treatment.For each strain (rows) and combination (columns) of a phenotype and a treatment (ate, iso1, iso10) the significance (signed -log10 value of Wilcoxon ranksum test, as used in Figure 4) of the phenotypic response with respect to the ctr group is shown using a colour code. Rows and columns are clustered according to pattern similarity. The branches of the dendrograms illustrating the clusters are plotted with the same colour as long as the average linkage distance is less than 50% of the maximal distance. AC: ate vs ctr; I1C: iso1 vs ctr; I10C: iso10 vs ctr. See Table 1 for abbreviations. HR std: standard deviation of HR (TC) strain means; SBP std: standard deviation of SBP strain means.
Mentions: Each drug treatment was assessed for its impact on the patterns of correlations across mean trait values or strains (see Suppl. Figures 5–7 in Supplement S1). The high correlations between HW, AW, VW and BWE were globally maintained also upon perturbations of the β-adrenergic system but were slightly reduced under iso10 as compared to ctr mice (i.e. 0.4<r<0.8; compare Suppl. Figures 6A and 6D in Supplement S1). High similarity of HW and VW with Pdur was still detected under β-stimulation (i.e. 0.5<r<0.8) but it was significantly reduced under ate (r = 0.19, p = 0.38). Again and irrespective of the drug condition, no significant correlation could be identified between HR and SBP, between HR and VWI or AWI, and between SBP and AWI or VWI.

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