ABSTRACT
Mouse developmental pathology assessments are commonly conducted to discern whether a particular experimental manipulation has affected anatomic, biochemical, and/or functional attributes in one of two settings. The rst is to dene whether or not animals having different genotypes exhibit divergent phenotypes. In the simplest case, involving a single gene with only two possible alleles (normal [+] or altered [−]), the three possible genotypic groups would be wild-type (+/+), heterozygous (+/−), and homozygous mutant (−/−). A variant of this scenario is the case where one cohort of animals has been genetically engineered to overexpress a foreign molecule, yielding a transgenic genotype (+), which will be compared to nontransgenic (−) mice that do not carry the transgene. The second instance involves distinguishing between the structure and/or function of mice that were exposed to some agent or manipulation (i.e., treated animals) versus others who were not subject to the same exposure (i.e., control animals). A standard design for this latter scenario is to treat pregnant dams with a xenobiotic (or test article) in a conventional developmental toxicity study, which typically uses four doses: none (vehicle only), low, middle, or high. In both settings, conclusions drawn with respect to the biological outcomes need to be interpreted with respect to their biological relevance. The general means for reaching such conclusions is rst to perform an appropriate statistical analysis to evaluate the effects related to distinct genetic backgrounds or different doses of the xenobiotic treatment and then to determine whether or not any statistically signicant effects also are biologically plausible.
