, 5–28 (2008)doi:10.1093/toxsci/kfn121Advance Access publication June 19, 2008
: An Emerging Model in Biomedical andEnvironmental Toxicology
Maxwell C. K. Leung,* Phillip L. Williams,
Kirsten J. Helmcke,
and Joel N. Meyer*
*Nicholas School of the Environment, Duke University, Durham, North Carolina 27750;
Department of Environmental Health Science, College of PublicUniversity of Georgia, Athens, Georgia 30602; and
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37240
Received April 30, 2008; accepted June 10, 2008
has emerged as animportant animal model in various ﬁelds including neurobiology,developmental biology, and genetics. Characteristics of thisanimal model that have contributed to its success include itsgenetic manipulability, invariant and fully described developmen-tal program, well-characterized genome, ease of maintenance,short and proliﬁc life cycle, and small body size. These samefeatures have led to an increasing use of
in toxicology,both for mechanistic studies and high-throughput screeningapproaches. We describe some of the research that has beencarried out in the areas of neurotoxicology, genetic toxicology, andenvironmental toxicology, as well as high-throughput experimentswith
including genome-wide screening for moleculartargets of toxicity and rapid toxicity assessment for newchemicals. We argue for an increased role for
incomplementing other model systems in toxicological research.
Key Words: Caenorhabditis elegans
; neurotoxicity; genotoxicity;environmental toxicology; high-throughput methods.
is a saprophytic nematode speciesthat has often been described as inhabiting soil and leaf-litter environments in many parts of the world (Hope, 1999); recent reports indicate that it is often carried by terrestrial gastropodsand other small organisms in the soil habitat (Caswell-Chen
, 2005; Kiontke and Sudhaus, 2006). Although scientiﬁcreports on the species have appeared in the literature for morethan 100 years (e.g., Maupus, 1900), the publication of Brenner’s seminal genetics paper (Brenner, 1974) signaled itsemergence as an important experimental model. Work with
has since led in a short time span to seminaldiscoveries in neuroscience, development, signal transduction,cell death, aging, and RNA interference (Antoshechkin andSternberg, 2007). The success of
as a model hasattracted increased attention as well in the ﬁelds of inbiomedical and environmental toxicology.Clearly,
will be a valuable toxicity model only if its results were predictive of outcomes in higher eukaryotes.There is increasing evidence that this is the case both at thelevel of genetic and physiological similarity and at the level of actual toxicity data. Many of the basic physiological processesand stress responses that are observed in higher organisms(e.g., humans) are conserved in
. Depending on thebioinformatics approach used,
homologues havebeen identiﬁed for 60–80% of human genes (Kaletta andHengartner, 2006), and 12 out of 17 known signal transductionpathways are conserved in
and human (NRC, 2000;Table 1). We discuss speciﬁc examples in the areas of neurotoxicology and genetic toxicology in this review.
has a number of features that make it not just relevant but quite powerful as a model for biologicalresearch. First of all,
is easy and inexpensive tomaintain in laboratory conditions with a diet of
.The short, hermaphroditic life cycle (
3 days) and large number (300
) of offspring of
allows large-scale productionof animals within a short period of time (Hope, 1999). Since
assayscanbeconductedin a 96-well microplate. The transparent body also allows clear observation of all cells in mature and developing animals.Furthermore, the intensively studied genome, complete celllineage map, knockout (KO) mutant libraries, and establishedgenetic methodologies including mutagenesis, transgenesis, andRNA interference (RNAi) provide a variety of options tomanipulate and study
at the molecular level (Tables 2and 3; for a more detailed presentation of genetic and genomicresources, see Antoshechkin and Sternberg, 2007). We addressthe particular power of these genetic and molecular tools in
at more length below.Since reverse genetic and transgenic experiments are mucheasier and less expensive to conduct in
To whom correspondence should be addressed at Nicholas School of theEnvironment, Box 90328, Duke University, Durham, NC 27708-0328.Fax: (919) 668-1799. E-mail: email@example.com.
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