TABLE 7-3 Advantages and Disadvantages of Four Model Animals for Toxicant Testing

Organism

Advantages

Disadvantages

C. elegans

Relatively inexpensive, short life cycle, small size, large populations, extensive information on genetics, genomics known

Some signaling pathways are apparently not represented (e.g., Hedgehog); short life cycle, so test compounds might persist long enough to complicate the study of sensitive developmental periods and of primary versus secondary effects

Drosophila

Relatively inexpensive, short life cycle, small size, large populations, extensive information on genetics, genomics known

During pupal development organism is inaccessible to toxicants; short life cycle, so test compounds might persist long enough to complicate the study of sensitive developmental periods and of primary versus secondary effects

Zebrafish

Simple vertebrate, transparent, external embryos, best organogenesis model

Relatively expensive, long life cycle, genetics and genomics research in progress

Mouse

Mammalian model, most similar to humans, targeted gene replacement possible

Relatively expensive, long life cycle, embryonic development in utero and not as easily accessible for manipulation as other model animals

Comparative Utility of Model Organisms

In summary, each of the four genetically tractable model organisms—C. elegans, Drosophila, zebrafish, and mouse—offers promise for development of tests to identify potential developmental toxicants, and each has advantages and disadvantages, as summarized in Table 7-3.

A useful approach, which the committee will present more fully in Chapter 8, might be to develop the more-rapid and inexpensive systems, namely, C. elegans and Drosophila, for preliminary large-scale assays, which can be followed up by more definitive tests using the vertebrate models, zebrafish and mouse, which, although slower and more costly, are more likely to give results relevant to humans.

GENE EXPRESSION AS DETERMINED BY IN VITRO AND ENGINEERED CELL TECHNOLOGIES

Mammalian cells in culture, as an inexpensive and fast complement to whole-animal (e.g., mouse and rat) studies, can be used for a wide variety of specific



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