PUBLICATION

Aging-associated sinus arrest and sick sinus syndrome in adult zebrafish

Authors
Yan, J., Li, H., Bu, H., Jiao, K., Zhang, A.X., Le, T., Cao, H., Li, Y., Ding, Y., Xu, X.
ID
ZDB-PUB-200514-7
Date
2020
Source
PLoS One   15: e0232457 (Journal)
Registered Authors
Ding, Yonghe, Xu, Xiaolei
Keywords
none
MeSH Terms
  • Aging/genetics*
  • Aging/physiology*
  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal
  • Electrocardiography
  • Humans
  • Mice
  • Models, Cardiovascular
  • Mutation, Missense
  • NAV1.5 Voltage-Gated Sodium Channel/genetics
  • Sick Sinus Syndrome/etiology*
  • Sick Sinus Syndrome/genetics
  • Sick Sinus Syndrome/physiopathology
  • Sinus Arrest, Cardiac/etiology*
  • Sinus Arrest, Cardiac/genetics
  • Sinus Arrest, Cardiac/physiopathology
  • Species Specificity
  • Zebrafish/genetics*
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
PubMed
32401822 Full text @ PLoS One
Abstract
Because of its powerful genetics, the adult zebrafish has been increasingly used for studying cardiovascular diseases. Considering its heart rate of ~100 beats per minute at ambient temperature, which is very close to human, we assessed the use of this vertebrate animal for modeling heart rhythm disorders such as sinus arrest (SA) and sick sinus syndrome (SSS). We firstly optimized a protocol to measure electrocardiogram in adult zebrafish. We determined the location of the probes, implemented an open-chest microsurgery procedure, measured the effects of temperature, and determined appropriate anesthesia dose and time. We then proposed an PP interval of more than 1.5 seconds as an arbitrary criterion to define an SA episode in an adult fish at ambient temperature, based on comparison between the current definition of an SA episode in humans and our studies of candidate SA episodes in aged wild-type fish and Tg(SCN5A-D1275N) fish (a fish model for inherited SSS). With this criterion, a subpopulation of about 5% wild-type fish can be considered to have SA episodes, and this percentage significantly increases to about 25% in 3-year-old fish. In response to atropine, this subpopulation has both common SSS phenotypic traits that are shared with the Tg(SCN5A-D1275N) model, such as bradycardia; and unique SSS phenotypic traits, such as increased QRS/P ratio and chronotropic incompetence. In summary, this study defined baseline SA and SSS in adult zebrafish and underscored use of the zebrafish as an alternative model to study aging-associated SSS.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping