Zebrafish General Information
Zebrafish (Danio rerio) is a small tropical freshwater fish native to the streams of the southeastern Himalayan region, which commonly inhabits slow-moving water bodies. It takes its name from the horizontal blue-pigmented stripes aligning its body, which are reminiscent of zebra stripes. Adult Danio rerio grows up to 4 cm, and their lifespan is between two to three years in standard laboratory conditions. Both size and age can be greater in their natural habitat.
Zebrafish are omnivorous, primarily eating zooplankton and insects, although they can eat a variety of other foods, such as worms, small crustaceans or algae. This is one of the characteristics that makes this freshwater fish an extremely robust animal model for the laboratory.
They reach sexual maturity at approximately three months. A male must be present to induce female ovulation and egg fecundation. Females can spawn at intervals of two to three days, laying more than two hundred eggs in each mating. Their ability to produce a vast number of progeny is another advantage of using this particular family of fishes in the laboratory.
On the release of the eggs, embryonic development begins. The zebrafish embryo develops quickly, with precursors of all significant organs appearing within 36 hours post-fertilization (hpf). The embryo starts as a yolk with a single enormous cell on top; this divides into two and continues dividing until there are thousands of small cells. The cells then migrate down the sides of the yolk and begin forming a head and tail, which later grow and separate from the body. From 4 dpf, heart physiology is stable; from 5 dpf they respond to optical, tactile and acoustic stimuli and display free swimming, which suggests a sophisticated nervous system; also from 5 days, the digestive/excretory system is fully functional. Another very important feature is that zebrafish embryonic and larval tissues are optically transparent, which makes it possible to visualize morphogenetic movements and organs in vivo (ie heart beating).
The prolific production of offspring, rapid life cycle and morphological transparency are key features that make the zebrafish an ideal animal model for biomedical research and early drug discovery.
All the above advantages have meant that zebrafish have become an essential tool for high-throughput screening of small molecules with therapeutic effects. Accordingly, both academics and the pharmaceutical industry use zebrafish to save time and money in preclinical studies to assess toxicity and efficacy of new drugs in the fields of cardiovascular disease, neural disorders, infection, and cancer, amongst others.
In summary, the features that make zebrafish suited to research are multiple:
- Drugs are administered directly in the swimming water. This has two main advantages; firstly, it considerably reduces the time needed for a procedure; when compared with the time invested in injecting drugs into mice for example. Secondly, it is much better adapted to understanding how a molecule behaves in terms of ADME (Absorption, Distribution, Metabolism, and Excretion) in the context of a whole living animal, compared with its behavior in a biochemical or cell culture drug screening procedure, which by nature will provide much more limited information in this respect.
- The small size and the high number of the zebrafish progeny allow parallel and reproducible testing of several drugs and dosages in simple multi-well plates, and make it ideal for high throughput assays. In addition, the increased sample size helps with more accurate statistical analysis.
- Zebrafish share a high degree of conservation with humans in both their genome and their physiological processes. They have a similar genetic structure and share 70% of genes with us. Indeed, 82% of genes known to be associated with human disease have a zebrafish counterpart. As a vertebrate, the zebrafish has the same major organs and tissues as humans. This makes it possible to assess with certainty the possible toxicity, or effects that a drug could have when administered to people.
- The transparency of the Danio rerio larval stage, combined with a growing battery of fluorescent tissue-specific zebrafish transgenic lines and novel advances in image capture and processing makes it possible non-invasive in vivo analysis of the drug effects in both groups of cells and single tissues.
Taken together these features mean that zebrafish research has provided advances in the fields of developmental biology, oncology, toxicology, reproductive studies, teratology, genetics, neurobiology, environmental sciences, stem cell research and regenerative medicine, and even evolutionary theory. The list of fields in which the zebrafish model can be applied is still growing.