Danio rerio, commonly known as Zebrafish, is a small freshwater fish that has gained significant prominence as a New Alternative Model (NAM) for in vivo research, rivaling traditional animal models like rodents. This species offers a unique combination of characteristics that make it indispensable for developmental biology, genetics, and beyond.

This article aims to provide a comprehensive guide to Danio rerio, covering its biology, habitat, and importance in scientific research, followed by essential facts highlighting why this species is so valuable to the scientific community.

 

Complete Guide about Danio Rerio

 

Danio rerio is a tropical fish native to the streams and ponds of South-East Asia. Typically, adult Danio rerio grows to a length of about 2.5 to 4 centimeters and is easily identified by its distinctive horizontal blue and silver stripes, which give them their name.

One of the primary reasons Danio rerio has become a leading model organism in research is its speedy life cycle. They reach sexual maturity within three months and can spawn every two to three days, with each spawning a couple capable of producing up to 300 embryos. Unlike mammals, Danio rerio embryos develop outside the mother’s organism, which allows for easy manipulation and observation of various developmental stages, reducing the need for more hostile procedures.

The transparency of the embryos is also particularly useful for studying cellular and developmental biology as it enables the visualization of internal structures without the invasive handling of Zebrafish. This characteristic allows phenotypical screening of the developmental processes and cellular behaviors. 

Moreover, the use of fluorescent markers further enhances the utility of Zebrafish in research. Introducing fluorescent proteins enables specific cells, tissues, or proteins to precisely track gene expression and cellular movements within the transparent embryos. For example, it can be observed how specific genes are activated during development, how cells migrate to form different tissues, and how various signaling pathways operate in a living organism. The ability to perform live imaging of these processes in a vertebrate model is invaluable for understanding complex biological systems.

Genetically, Danio rerio is remarkably similar to humans. The Zebrafish genome, which has been fully sequenced, reveals that approximately 80% of Zebrafish genes have at least one human ortholog, and about 85% of genes associated with human diseases have a counterpart in Zebrafish. However, the genetic similarity extends beyond mere gene presence. Many fundamental biological processes and pathways are conserved between Zebrafish and humans, including those involved in development, cell signaling, and disease pathogenesis. This conservation enables Zebrafish to model complex human diseases, like cancer, cardiovascular diseases, and neurological disorders.

In addition to their biological and genetic attributes, the cost-effectiveness of Danio rerio research is another significant benefit. Maintaining Danio rerio in laboratory conditions is relatively feasible and cost-effective compared to mammalian models like mice. 

 

Essential Facts about Danio rerio for its Applications 

 

A critical advantage of using Zebrafish in research is their alignment with the 3Rs principles— Reducement, Refinement and Replacement—of animal experimentation. Zebrafish research reduces the reliance on higher animals, refines methods to minimize suffering, and replaces traditional models with species that can be studied in large numbers with fewer ethical concerns, particularly during their early developmental stages.

An ideal alternative in vivo model should merge the high-throughput and cost-effectiveness of in vitro methods with animal studies' detailed insights and reliability. Zebrafish effectively combine these benefits as a vertebrate model with high genetic similarity to humans and the fact that invitro tools can be implemented in this model with the benefit of also obtaining behavior data. They serve as a bridge between in vitro and in vivo models, offering a viable and cost-effective system for High-Content Screening Assays (HCS). Zebrafish embryos, in particular, support these assays with less ethical concerns associated with traditional in vivo studies, as they are not classified as animal models until 5-6 days post-fertilization (dpf) under European Animal Welfare Legislation (EU Directive 2010/63/EU). 

Its cost-efficiency, combined with high fecundity, ease of genetic manipulation, and high suitability with HCS, makes Danio rerio an attractive model for pharmacological studies during the Drug Discovery and Development process. Zebrafish enables the evaluation of both the efficacy and toxicity of new compounds before proceeding to further studies in mammalian models, particularly during the early stages of lead optimization in pre-clinical studies. This preliminary screening provides critical insights into the toxicity, safety, and efficacy of new drug candidates, significantly enhancing their chances of success in further stages of the Drug Development and Discovery process. The use of Danio rerio helps reduce the surplus of resources that would occur from directly testing less viable drugs in traditional animal models. This approach not only increases the efficiency of the whole Drug Development process but also aligns with ethical principles by reducing the number of animals used in preliminary assessments.

Moreover, another characteristic that makes Danio rerio particularly valuable for pharmacological studies is its high responsiveness to genetic manipulation. The development of advanced genetic tools, such as mRNA injections for impression of HA-tagged proteins and Transcription Activator like Effector Nucleases, has revolutionized the possibilities of editing the Danio rerio genome with high precision. This genetic versatility enables the study of complex genetic interactions and Zebrafish characteristics facilitate the study of resulting phenotypic effects, being a reliable model of human genetic disorders.

Toxicology and environmental science also heavily rely on Danio rerio as a model for assessing the effects of environmental pollutants and chemicals on biological systems. Zebrafish are highly sensitive to changes in water quality, making them a reliable indicator species for environmental monitoring. Studies using Zebrafish have provided crucial data on the health impact of various toxicants, including heavy metals and endocrine disruptors chemicals (EDC).

At Biobide, our expertise in Zebrafish drives our commitment to accelerate researchers' R&D process, ensuring the translation of scientific results into valuable contributions to human and environmental well-being.

Biobide’s endocrine disruption assays allow screening of the Thyroid Disrupting potential of chemical compounds with different parameters. It detects the maximum tolerated concentrations, relieves alterations in hormone levels by HPLC-Ms techniques, and tracks thyroglobulin levels by image analysis. Moreover, a gene expression analysis could be carried out to obtain a more extensive characterization of the thyroid disrupting effect of main genes related to EDCs.

Evaluating the impact of endocrine disruptors is essential for comprehending their influence on human hormonal systems, which are critical in regulating several body functions and maintaining overall health. Through these assessments, we can identify and mitigate potential risks associated with exposure to these chemicals, thereby promoting both human health and environmental protection.

 

 

Sources
 

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3. Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, et al. The zebrafish reference genome sequence and its relationship to the human genome. Nature. 2013;496(7446):498-503. 

4. Hill AJ, Teraoka H, Heideman W, Peterson RE. Zebrafish as a model vertebrate for investigating chemical toxicity. Toxicol Sci. 2005;86(1):6-19. 

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