Development of Mature Zebrafish as an Animal Model

     Fish Pathology

     Zebrafish (Danio rerio) have proved to be an outstanding animal model to explore vertebrate development. Ongoing activities in the zebrafish investigator community have resulted in a multitude of resources available to researchers using this animal model. For example, (1) there is a National Zebrafish Stock Center and (2) a variety of antibodies and cDNA libraries are available. Furthermore, the extensive genetic characterization that zebrafish have undergone, including the creation of YAC genomic libraries and microsatellite genetic linkage maps, provide a cutting edge ability to rapidly take advantage of this animal model. This wealth of resources has been under exploited for evaluation of biology or pathophysiology of mature zebrafish. Most scientists evaluate zebrafish at the embryonic/neonate stages after mutagenesis or toxin exposure. Thus, it is plausible that many mutation- or toxic-mediated effects that occur in late life will not be identified. It follows that a wealth of information with relevance to human biology and disease is being overlooked. The goal of the current project is to understand some aspects of the basic biology of aging zebrafish. To accomplish this, we will perform the following specific aims:
     I. Characterize zebrafish demography. Experienced zebrafish investigators estimate that the zebrafish lifespan is approximately two to four years. However a critical evaluation of median and maximum lifespan has not been performed. These data are requisite towards understanding the normal biology of zebrafish for comparative medicine purposes. To perform this, we will evaluate lifespan parameters in several strains of laboratory and wild caught zebrafish.
     II. Create an atlas of anatomy and age-associated histopathology of zebrafish. Evaluation of gross, histologic and clinical pathological changes that occur during aging in the zebrafish have not been systematically explored. To provide information about healthy animals and age-specific pathology, aging zebrafish will be sacrificed at 6-month intervals for anatomic and histologic evaluation. These images will be collated into an atlas that will be published and presented on the ZFIN website.
     III. Provide an example of the utility of mature zebrafish as animal model. It is well established that the aging process diminishes mammal?fs ability to adapt to environmental stress. This is manifested, in part, by decreased production of heat shock protein (HSP) in response to environmental stress. Thus, in order to demonstrate the utility of mature zebrafish as an animal model, we will explore the role of aging on HSP production. Accordingly, we will subject young and mature, and old zebrafish to both heat and ethanol stress and evaluate their mortality rates and their ability to activate HSP mRNA production.
     When this project is completed, we believe this animal model will be a powerful research tool for investigators whom explore research areas germane to a wide variety of NIH Institutes.

University of Michigan Medical School Urology Department