Document Detail


High-resolution cardiovascular function confirms functional orthology of myocardial contractility pathways in zebrafish.
MedLine Citation:
PMID:  20388839     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phenotype-driven screens in larval zebrafish have transformed our understanding of the molecular basis of cardiovascular development. Screens to define the genetic determinants of physiological phenotypes have been slow to materialize as a result of the limited number of validated in vivo assays with relevant dynamic range. To enable rigorous assessment of cardiovascular physiology in living zebrafish embryos, we developed a suite of software tools for the analysis of high-speed video microscopic images and validated these, using established cardiomyopathy models in zebrafish as well as modulation of the nitric oxide (NO) pathway. Quantitative analysis in wild-type fish exposed to NO or in a zebrafish model of dilated cardiomyopathy demonstrated that these tools detect significant differences in ventricular chamber size, ventricular performance, and aortic flow velocity in zebrafish embryos across a large dynamic range. These methods also were able to establish the effects of the classic pharmacological agents isoproterenol, ouabain, and verapamil on cardiovascular physiology in zebrafish embryos. Sequence conservation between zebrafish and mammals of key amino acids in the pharmacological targets of these agents correlated with the functional orthology of the physiological response. These data provide evidence that the quantitative evaluation of subtle physiological differences in zebrafish can be accomplished at a resolution and with a dynamic range comparable to those achieved in mammals and provides a mechanism for genetic and small-molecule dissection of functional pathways in this model organism.
Authors:
Jordan T Shin; Eugene V Pomerantsev; John D Mably; Calum A MacRae
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-04-13
Journal Detail:
Title:  Physiological genomics     Volume:  42     ISSN:  1531-2267     ISO Abbreviation:  Physiol. Genomics     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-08     Completed Date:  2010-10-28     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  9815683     Medline TA:  Physiol Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  300-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Animals
Cardiovascular Physiological Phenomena
Embryo, Nonmammalian / physiology
Heart / embryology,  physiology*
Models, Animal
Myocardial Contraction / physiology*
Myocardium / metabolism*
Phenotype
Zebrafish / embryology,  metabolism,  physiology*
Grant Support
ID/Acronym/Agency:
GM-075946/GM/NIGMS NIH HHS; HL-085280/HL/NHLBI NIH HHS; K08 HL085280/HL/NHLBI NIH HHS; K08 HL085280-03/HL/NHLBI NIH HHS; R01 HL109264/HL/NHLBI NIH HHS; R21 HL098938/HL/NHLBI NIH HHS
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