Zebrafish: A Model Organism for Biomedical Research.

As a model organism for the study of vertebrate development, disease, biological pathways, and toxicological mechanisms, the zebrafish (Danio rerio) has a number of advantageous features. It is a vertebrate with organs similar to those of man. Zebrafish embryos develop outside the mother and without an eggshell, and the transparency of the developing embryo allows one to trace the movement of individual cells and thereby follow the development of organs such as the skin, bone, muscle, heart, and kidney, and the circulatory, hematopoietic, and central nervous systems.

The zebrafish is a small aquarium species with the potential for thousands of offspring from a single female. The most powerful and unique feature of the zebrafish is that it is a vertebrate model organism in which large-scale forward mutagenesis screens can be performed with relative ease. There are mutations available in over 2,000 genes essential for embryonic development in zebrafish. Early development of human embryos, including patterning of the neural tube, many aspects of behavior, hematopoiesis, and development of the heart, circulatory system, brain, body axis, ear, liver, and kidney are highly similar in zebrafish and human embryos. The genes that actually regulate zebrafish development have close relatives that direct similar processes in human development and organ function.

The large-scale saturation genetic screens of zebrafish will also provide a strong underpinning to the Environmental Genome Project (http://www.niehs.nih.gov/envgenom/home.htm). Research on genetic phenotypes of zebrafish will vastly increase the translation of human sequence data to human gene function because the phenotype of the zebrafish mutations will suggest a function of the similar human gene. In addition, characterization of genes responsible for mutant phenotypes may identify genes involved in human diseases and toxic responses and may be useful for testing potential therapies and interventions.

The Trans-NIH Zebrafish Coordinating Committee consists of representatives from 18 NIH institutes and centers, including the NIEHS. The goal of this group is to facilitate and coordinate zebrafish research. Over the last three years this group held two workshops and released two requests for applications and one program announcement to facilitate zebrafish research. The NIH has a Web site for model organisms for biomedical research, located at http://www.nih.gov/science/models/, that includes a zebrafish Web page.

Contact: Jerry Heindel, Scientific Program Administrator, e-mail: [e-mail].