Zebrafish as Model for Human Disease

Zebrafish have been used extensively in a variety of medical and scientific disciplines including cardiology, neurology, ophthalmology, and environmental toxicology. However, the majority of these studies have explored developmental aspects. Studies in mature zebrafish, and even their normal anatomy, have been largely unexplored, though they have tremendous potential as animal models for diseases that occur later in life. Their small size makes

Figure 27.2. Sagittal section of zebrafish. This demonstrates a reconstruction of several individual sections of a zebrafish to create a high-resolution sagittal section. Stained with hematoxylin and eosin.

Figure 27.2. Sagittal section of zebrafish. This demonstrates a reconstruction of several individual sections of a zebrafish to create a high-resolution sagittal section. Stained with hematoxylin and eosin.

zebrafish amenable to rapid histological analysis (Figure 27.2).

We must understand their normal anatomy in order to detect pathology. In terms of serving as animal models for human disease, there are several examples. For instance, the recent cloning of the Huntington's disease gene homologue in zebrafish (Karlovich et al., 1998) has broad implications for the importance that a mature zebrafish model may provide towards understanding this disease's pathophysiology. A mutation in vHnf1 has also been recently cloned in zebrafish, which is orthologous to a gene mutated in human polycystic kidney disease (PKD) (Sun et al., 2001). As in human disease, this zebrafish mutant forms cysts in its kidneys, representing a potential model of human glomerulocystic kidney disease. Zebrafish have also been found to express amyloid precursor protein (APP), presenilin (PS)-1, and apolipoprotein E (apoE), which have all been implicated in familial Alzheimer's disease (FAD) (Leimer et al., 1999; Monnot et al., 1999). Zebrafish PS-1 has been found to promote aberrant secretion of Abeta42 similar to FAD-associated PS1 mutations (Leimer et al., 1999). Zebrafish have been proposed as an ideal vertebrate system in which to model cancer as well (Amatruda et al., 2002; Stern et al., 2003). Thus, the mature zebrafish has tremendous potential as a model of adult and late-life human diseases.

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Blood Pressure Health

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