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. Author manuscript; available in PMC: 2013 Jun 11.
Published in final edited form as: Circ Res. 2011 Sep 16;109(7):794–806. doi: 10.1161/CIRCRESAHA.111.244897

Table I. Comparison of Model Systems of Cardiovascular Diseases.

The strengths and limitations of fly, zebra fish, mouse, and large animal models of cardiovascular diseases are shown.

Model Advantages Disadvantages
Fly
  • -

    Short life cycle

  • -

    Balancer chromosomes

  • -

    Easily observed physical traits

  • -

    Low maintenance costs

  • -

    Well-annotated databases

    • Flybase.org

    • Bloomington

  • -

    Gal4/UAS bipartite transgenic system permits transgene expression under tissue and temporal control

  • -

    Extensive Genetic/Genomic Resources

    • Chemically mutated stocks

    • P-element mutants

    • Molecularly-defined genomic deficiencies

    • Transgenic RNAi lines

  • -

    Amenable to high-throughput suppressor/enhancer and drug screens

  • -

    Lacks genetic redundancy of more complex organisms (more efficient evaluation of candidate genes with respect to number of gene knockdowns and time of analyses)
  • -

    Single chamber open circulatory system

  • -

    No coronary circulation (oxygen transport by diffusion)

  • -

    Two pacemakers and irregularities in adult heart rate can make assessment of arrhythmia difficult in intact flies

  • -

    Lacks genetic redundancy of more complex organisms (the fly may lack specific gene regulatory mechanisms that are present in mammalian systems)
Zebrafish
  • -

    Well-developed resources for lineage tracing, transgenic expression, and knockdown with morpholinos

  • -

    Two chambered heart with distinct atrium and ventricle

  • -

    Cardiac conduction system has similarities to mammals

  • -

    Amenable to large scale drug studies

  • -

    Heart has regenerative capacity
  • -

    Imaging the cardiac chamber can be challenging given the highly trabeculated ventricle

  • -

    Costs associated with maintaining stock

  • -

    Mapping new mutants can be difficult
Mouse
  • -

    Four chambered heart is similar to humans

  • -

    Conduction system is similar to humans

  • -

    Amenable to measurement of cardiac physiology

    • Intra-cardiac hemodynamic measurements

    • Intra-cardiac electrophysiology testing

    • Trans-aortic constriction pressure overload

    • Coronary ligation/Ischemia-reperfusion studies

  • -

    Well-developed transgenic systems (overexpression/gene knock-out/gene replacement by homologous recombination)

  • -

    Quantitative trait loci (QTL) mapping

  • -

    Congenic strains
  • -

    Costs associated with maintaining mouse colonies

  • -

    Breeding time to develop complex genetic crosses

  • -

    Difficult to perform high-throughput forward genetic screens
Large Animal (pig/rabbit/sheep/dog)
  • -

    Four chambered heart is similar to humans

  • -

    Conduction system is similar to humans

  • -

    Amenable to measurement of cardiac physiology

    • Intra-cardiac hemodynamic measurements

    • Intra-cardiac electrophysiology testing

    • Trans-aortic constriction pressure overload

    • Coronary ligation/Ischemia-reperfusion studies

  • -

    Well suited for developing surgical techniques/delivery of Therapeutics
  • -

    Difficult to perform genetic loss of function studies