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Zebrafish

 Zebrafish in an aquariumThe zebrafish (Danio reiro) has many features which make it an excellent model organism for studying development in vertebrates. The embryos develop externally to the mother and are transparent, so they can be easily viewed and manipulated.Compared to frogs the organization of the zebrafish embryo is simple, and they develop more quickly. Zebrafish grow to maturity and are able breed within 2 to 3 months. They also produce large numbers of offspring – a female zebrafish can lay up to 200 eggs a week.

Like the mouse, the zebrafish is suitable for genetic analysis, and is a valuable tool for creating genetic models of human diseases. The sequencing of the zebrafish genome began in 2001, and is currently ongoing.ANCHOR Although the zebrafish genome is only half the length of the human genome, the genetic structure is remarkably similar. Genes responsible for human diseases often have equivalents in the zebrafish.

Creating transgenic models
Leukaemia
The development of the heart
References

Creating transgenic models

It is easy to produce mutations in zebrafish, and screening programmes have been developed to find mutations which affect particular biological systems, such as the development of the nervous system. Transgenic zebrafish were cloned from cells cultured for three months in 2002.ANCHOR Zebrafish mutants are currently used to model many human diseases, including Alzheimer’s disease, congenital heart disease, polycystic kidney disease and some cancers.

ZF-models – zebrafish models for human disease is a project funded by the European commission, which began in 2004. Its aim is to use the zebrafish to produce new disease models, find new drug targets and learn more about the gene-regulation pathways involved in human development and disease. Among its research the project aims to produce 180 knockout strains of zebrafish, which will help understanding and modeling of human diseases.

Leukaemia

Using genetic techniques, a team of researchers stimulated the development of a type of leukaemia - T cell acute lymphoblastic leukaemia - in the fish.ANCHOR They fused the gene Myc, which plays an important role in human leukaemia and lymphoma, to a zebrafish gene that works exclusively in lymphoid cells - which become diseased in leukaemia. They then tagged the fused gene with a third gene which caused leukaemia cells to glow green under fluorescent light, so they could observe the cancer as it progressed. The three-gene combination was then injected into embryonic zebrafish, so that the genes were incorporated in all developing fish cells. Cancer developed in virtually all fish that carried a functional Myc gene.

Creating zebrafish which develop leukaemia will enable researchers to screen thousands of zebrafish genes for mutations that contribute to the disease, and to test the effect of various anti-cancer agents.

The development of the heart

The transparent zebrafish embryo allowed researchers to study its beating heart, predicting that certain blood flow patterns in the organ are key to its normal, healthy development.ANCHOR After measuring the velocities and patterns of blood flow, the team calculated the expected forces imposed on the heart chamber walls by the flowing blood. They surgically blocked the incoming or outgoing blood flow and found that when flow was reduced, the smaller forces on the heart wall resulted in drastically altered development in the chambers, valves and orientation of the heart. Many of these changes were similar to those seen in cases of congenital heart disease and in zebrafish lacking key genes for heart development. The early development of the heart is similar in all vertebrates and these findings are likely to also be true of human embryos.


References

  1. Wellcome Trust Sanger Institute, The Danio rerio Sequencing Project http://www.sanger.ac.uk/Projects/D_rerio/, accessed 18.03.2008
  2. K-Y Lee et al. Cloned zebrafish by nuclear transfer from long-term-cultured cells, Nat. Biotechnol. 20 (8), 795-799
  3. David M. Langenau et al. (2003) Myc-Induced T Cell Leukemia in Transgenic Zebrafish, Science 299 (5608): 887-890.
  4. J. R. Hove et al. (2003) Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis, Nature 421, 172-177

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