OVERVIEW
   Zebrafish (Danio rerio) has emerged recently as a premiere organism to study vertebrate development and genetics. Powerful techniques allow efficient generation and recovery of zebrafish mutations. Ongoing genetic screens have identified over 7,000 mutations in zebrafish affecting genes that regulate developmental patterning, organogenesis, physiology and behavior. The functions of many of these genes are conserved among vertebrate groups. Thus, analysis of zebrafish mutations provides insights into gene functions in other vertebrates, including humans.

   The mission of the Zebrafish International Resource Center is to provide a central repository for wild-type and mutant strains of zebrafish and for materials and information about zebrafish research. Materials and zebrafish strains are distributed to the research community. Pathology services are provided for diseased fish. Standards and procedures for maintaining healthy strains of zebrafish are being developed and a manual for prevention, diagnosis, and treatment of diseases affecting zebrafish is being prepared.

   Recently, a small group of representatives of the zebrafish research community obtained funds to establish an International Resource Center for Zebrafish on the University of Oregon campus. These include money from the State of Oregon for construction of a new building and grants from the NIH for construction, equipment, supplies and operating expenses.

The Resource Center has three main functions:

1. It maintains and makes available to the research community wild-type and mutant zebrafish stocks, frozen sperm, and reagents. It organizes genetic markers and maintains the genetic map.
2. The Resource Center distributes information. It maintains the ZFIN computer database, accessible via the Internet, publishes a manual for the laboratory use of zebrafish, facilitates communication among zebrafish researchers, and hosts visits from researchers to work with stocks or learn techniques to identify and maintain mutants.
3. The Resource Center develops methods to improve zebrafish health. It establishes standards and procedures for generating and maintaining healthier more vigorous strains, characterizes endemic diseases, develops methods for disease control and treatment, and publishes a manual of procedures for preventing, diagnosing, and treating zebrafish diseases.

SPECIFIC AIMS

   The last several years have witnessed an explosion in our understanding of vertebrate development, largely based on work from a few model genetic organisms. The zebrafish is the newest of these model organisms. Because the basic principles of body patterning appear similar during embryogenesis of all vertebrates, insights gained from work on embryonic zebrafish has implications for human health and disease. Moreover, research on this organism meets the intent of the Animal Welfare Act because use of many higher vertebrates can now be replaced by use of this lower vertebrate.

   Systematic genetic research on zebrafish began at the University of Oregon and for many years Eugene was the only place it was performed. Recently, however, international interest in this organism has grown tremendously (Balter, 1995; Eisen, 1996; Travis, 1996); studies of the embryology and genetics of zebrafish and the recent identification of over 7,000 genetic mutations have led to a dramatic increase in the number of laboratories using this organism to study the basic mechanisms of vertebrate development. Until recently these genetic stocks were distributed among more than 100 laboratories in 28 countries. To make room for new mutants, laboratories must discontinue some of their current stocks many of which are permanently lost. The zebrafish research community desperately needed a centralized site to preserve and keep track of these stocks and to facilitate their distribution to researchers, thus supporting and promoting research opportunities while preventing duplication of effort.

The Zebrafish International Resource Center is a facility to maintain wild-type and mutant stocks of zebrafish and to make these stocks widely available to the international research community. The Resource Center reduces the requirement of individual laboratories to maintain stocks they are unable to study, it can provide animals at lower cost than individual laboratories, and most importantly, it can ensure the highest possible levels of quality and uniformity. Specifically we will:

1. Establish a Resource Center to serve as a central repository for materials and information.
   • The Resource Center maintains healthy stocks of fish and frozen sperm of identified genotypes and makes them widely available to the research community. The Resource Center obtains carriers of mutations from the research community and breeds them to produce new generations. The Center freezes and stores sperm from these carriers. It receives and stores antibodies, gene probes, and markers used to identify and analyze wild-type and mutant stocks. It receives and organizes genetic markers and maintains the genetic map. Upon request the Resource Center will ship these materials to research laboratories throughout the world.
2. Make information widely available to the research community.
   • The Resource Center maintains a computer database, accessible via the WWW of the Internet, of information about the stocks. Additionally, the database provides information about the genetic map, markers, molecular probes, laboratory methods, developmental staging, embryonic and adult anatomy, and gene expression patterns. Electronic links to researchers, laboratories, sources, and publications are provided through WWW services. The Resource Center fosters an electronic network of communication among laboratories using zebrafish. It publishes both hardcopy and electronic versions of a manual for the laboratory use of zebrafish and a periodical with news about zebrafish research and techniques. The Resource Center hosts visits from researchers who wish to work with stocks, learn techniques, or learn to identify and maintain mutant stocks.
3. Develop methods for improving health.
   • The Resource Center establishes standards and procedures for generating and maintaining healthier and more vigorous strains. It characterizes diseases endemic to laboratory stocks. The Resource Center studies these diseases to identify their sources and causes and develops methods for their control and treatment. The Resource Center publishes a manual for the prevention, diagnosis, and treatment of diseases affecting zebrafish.

REFERENCES

• Balter, M. (1995) In Toulouse, the weather-and the science-are hot. Science 269:480-481.
• Eisen, J.S. (1996) Zebrafish make a big splash. Cell 87:969-977.
• Travis, J. (1996) Gone Fishing! Scientists use mutant zebra fish to learn how vertebrate embryos develop. Science News 150:360-361.