Zebrafish Disease Models

Zebrafish (Danio rerio) has been extensively widely used as an animal model in various fields of biomedical research. The transparency of the zebrafish embryo enables real-time visualization of the development and morphogenesis of almost all of its tissues and organs. Zebrafish are amenable to genetic manipulation, for which advanced genetic and molecular techniques are constantly being introduced. A pair of adult zebrafish can produce hundreds of eggs in a single clutch, and the resulting embryos and larvae are sufficiently small that they can be housed in 96-well or 384-well plates, allowing phenotypic analysis by high-throughput microscopy and behavioral analysis systems.

Zebrafish has many physiological and genetic similarities with humans, including the brain, digestive tract, vasculature, musculature, and innate immune system. The cloning of mutated genes screened for specific phenotypes in zebrafish has similarities in humans and thus serves as a model for human disease and to study underlying mechanisms. Multiple other mutants that show phenotypic similarities to human disease have been screened and identified. These include neurological disorders, cardiovascular diseases, hematological disorder, muscle disease and cancers, anxiety, Parkinson’s disease, and posttraumatic stress disorder.

Figure 1. Zebrafish as a model for vertebrate development and human diseases.

Our Zebrafish Disease Models

Creative Biogene, a zebrafish research company with experienced scientists and advanced technology, has established a wide range of working zebrafish models to support multiple therapeutic/disease areas. Our zebrafish models provide insight into the pathogenesis of human disease and the related drug discovery and toxicology, and to allow the evaluation of novel small-molecule inhibitors. Various approaches have been used to model human genetic diseases in zebrafish at Creative Biogene.

Generation of stable zebrafish disease models

Random mutagenesis: Genetic manipulation of zebrafish has focused on random mutagenesis by chemical mutagens or retroviral-mediated insertional methods.
Targeted gene-editing: Powerful methods involving the use of engineered nucleases, including Z FNs, TALENs and CRISPR-Cas9 system have been employed to generate stable models of human disease, enabling targeted mutations to be created in specific zebrafish orthologues of interest. Besides, the CRISPR/Cas9 system is the preferred tool for generating zebrafish stable models of human genetic diseases at Creative Biogene.

Generation of transient zebrafish disease models

Morpholino knockdown: This has been accomplished via morpholino-mediated knockdown of zebrafish orthologues of interest. Allows for rapid examination of loss-of-function (LOF) phenotypes.
CRISPR/dCas9 (CRISPR interference): CRISPR interference (CRISPRi), another variation on the CRISPR/Cas9 system, can be used to reversibly silence the expression of a target gene at the transcriptional level. It can be used to model both LOF and gain phenotypes. It possesses the potential to be used on a large scale.

OUR DISEASE AREAS

References

Sassen W A, K?ster R W. A molecular toolbox for genetic manipulation of zebrafish. Advances in Genomics and Genetics, 2015, 5: 151.
Adamson K I, et al. Use of zebrafish models to investigate rare human disease. Journal of Medical Genetics, 2018, 55(10): 641-649.
Khan F R, Alhewairini S S. Zebrafish (Danio rerio) as a model organism. Current Trends in Cancer Management. IntechOpen, 2018.
Bradford Y M, et al. Zebrafish models of human disease: gaining insight into human disease at ZFIN. ILAR journal, 2017, 58(1): 4-16.

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