Biomedical Engineering Reference
In-Depth Information
pharmaceutical industry, but with different purposes. We have focused on devel-
oping screening methods for identifying and prioritizing the types of environmental
chemicals of concern for the U.S. EPA in estimating risks to the human population.
12.4 ZEBRAFISH MODELS
Zebrafish have become a popular organism in ecological research (Magalhaes
et al., 2007; Gunnarsson et al., 2008; Scholz et al., 2008; Seok et al., 2008), in addition
to their increasing use as a model organism in toxicological, pharmacological, and
biomedical research (reviewed in Hill et al., 2005; Rubinstein, 2006; Kari et al., 2007;
Barros et al., 2008; Peterson et al., 2008; Scholz et al., 2008). There are many
advantages of working with zebrafish, especially during development. Large stocks of
fish can be maintained due to their small size and relatively simple husbandry
requirements. Each mating of zebrafish can produce potentially hundreds of eggs,
which can be raised in the small wells of microtiter plates. The embryos and larvae
are also transparent, allowing detailed observation of their internal development.
Development progresses rapidly, making the study of large numbers of chemicals
practicable. In addition, direct exposure of the embryos eliminates the potential
confounding influence of maternal toxicity that can occur with mammalian models.
Finally, selective breeding and gene manipulation techniques have provided a broad
array of strains for probing the mechanisms of organ system development and disease
(Fetcho and Liu, 1998; Grunwald and Eisen, 2002; Lieschke and Currie, 2007).
The growing use of zebrafish in toxicology and pharmacology has highlighted the
need for a firm understanding of their behavior. Behavioral studies with developing
zebrafish may seem to pose greater difficulties than those encountered with adult fish,
due to their small size and rapid development. It is these very properties, however, that
make the larvae an attractive alternativemodel for assessing developmental toxicity in
a screening context. For example, individual zebrafish can be monitored in the small
wells of microtiter plates that are standard issue in biochemistry laboratories using
miniaturized assays. Considerable research is now available on the effects of
chemicals on zebrafish raised and tested in 96-well plates. Advances in studying
zebrafish behavior have also benefited from automated testing procedures for
studying locomotion, reflexes, sensory capacity, circadian rhythms, and learning
andmemory (see Fetcho and Liu, 1998; Orger et al., 2004; Lieschke and Currie, 2007;
Levin and Cerutti, 2008; MacPhail et al., 2009 for references). Most of these tests rely
on optical recording of behavior, followed by analysis using commercial data
software programs.
Despite the rise in popularity of behavioral studies on zebrafish, a cautionary
note is in order. Behavior occupies a unique niche in biology, including toxicology.
Damage to internal organs can result in behavioral change, but so can the
environmental conditions in which the behavior occurs. The main function of
behavior is to allow an organism to adapt to the ever-changing conditions of its
environment. A failure to understand and appreciate the mutual influence of the
intrinsic (i.e., organ system) and the extrinsic (i.e., environmental) forces on
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