MagHelix™ Zebrafish Screening Platform

Zebrafish (Danio rerio) possesses the physiology complexity of mammalian animals and is one of the most common vertebrate model organisms. Creative Biostructure establishes the MagHelix™ Zebrafish Screening Platform for medical research. Zebrafish is an excellent choice to model various diseases and screen novel drugs for medical and therapeutic research. Zebrafish larvae have been used increasingly within the last decade to assess the effects of chemical compounds.

Phenotype-based chemical screening in zebrafish.  Figure 1. Phenotype-based chemical screening in zebrafish.

Advantages of the Zebrafish as Animal Model

  • Small size makes their embryos and larvae dispensed in microtiter plates and ease to manipulate.
  • Zebrafish has high fecundity so it is easy to obtain large sample numbers.
  • Embryo and larvae are transparent to facilitate noninvasive imaging, enabling massive phenotype-based screening.
  • High genetic homology to humans (> 85%) as well as significant similarities in organogenesis and functional mechanisms.
  • The occurrence of numerous pathological processes is similar to those of many human diseases.
  • There are few ethical issues associated with the use of larvae up to the feeding stage.
  • They have permeability to small molecules which allows drug to administrate by immersion.
  • Small amount of sample is enough.
  • Short period for experiment.
  • Applications of the zebrafish as an animal model include both identification of endpoints of toxicity and elucidation of mechanisms of toxicity.

There are four classes of zebrafish chemical screening assays:

  • Morphological screens (to screen chemical genetics and toxicology)
  • Behavioral screens (ex. using swimming kinetics to quantify the effects of single compounds)
  • Fixed time-point/labeling assays (to obtain information on a cellular or tissue level)
  • Fluorescence assays (reporter-based quantifications)

Introduction to MagHelix™ Zebrafish Screening Platform

Using the zebrafish as animal model is the feature of this platform. The main research fields of the platform are: 1) Generating multiple transgenic zebrafish models for human disease; 2) Research and development of drug candidates based on screening results.

There are various assays based on MagHelix™ Zebrafish Screening Platform shown in the following table. Take the cardiovascular toxicity test as an example, which is a key limiting factor in drug discovery. One of the features that the zebrafish heart can be dissected rapidly and maintained ex vivo for several days makes zebrafish an excellent model for assessment of cardiovascular toxicity.

Angiogenesis assay
mRNA expression marker (Each gene)
Toxicity testsGeneral toxicity on survival rates of zebrafish embryo or larvae
Cardiotoxicity test in zebrafish
Toxicity test to development of motor neuron or dopaminergic neuron in zebrafish
Human Endothelial Cell (HUVEC) modelProliferation assay
Adhesion assay
Migration assay
Tube formation assay
Tg (Fli-1: EGFP) and Tg (Fli-1: nEGFP) transgenic zebrafish modelNormal angiogenesis assay in larvae
Tg (Fli-1: EGFP) zebrafish fin regeneration model
Regenerative angiogenesis assay in adult zebrafish
Neurological disorder modelProtective effect against H2O2 induced PC12 cell damage
Protective effect against H2O2 induced SH-SY5Y cell damage
Protective effect against L-glutaric acid (LGA) induced neuron cell death in zebrafish
Protective effect against MPTP or 6-OHDA induced dopaminergic neuron cell death in zebrafish (Parkinson’s disease)
Protective effect against MPTP or 6-OHDA induced deficit of locomotor behavior in zebrafish (Parkinson’s disease)
Protective effect against chemical-induced epilepsy in zebrafish
Cardiovascular disease modelProtective effect against chemotherapy drug-induced cardiac damage in zebrafish
Protective effect against chemical-induced cerebral hemorrhage in zebrafish
Skeletal disease modelBone anabolic effect in zebrafish
Immunological modelImmunosuppressive effect on T-cell in zebrafish

Creative Biostructure welcomes global academic institutions, biotechnology, and pharmaceutical industries to utilize our MagHelix™ Zebrafish Screening Platform to evaluate the activity and toxicity of compounds for drug development.

References

  1. Taylor K L.; et al. Small molecule screening in zebrafish: an in vivo approach to identifying new chemical tools and drug leads. Cell Communication and Signaling. 2010, 8(1): 11.
  2. Mathias J R.; et al. Advances in zebrafish chemical screening technologies. Future Medicinal Chemistry. 2012, 4(14): 1811-1822.
  3. Kitambi S S.; et al. Small molecule screening platform for assessment of cardiovascular toxicity on adult zebrafish heart. BMC Physiology. 2012, 12(1): 1-7.

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