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Effects of heredity on response to drugs and environmental chemicals: construction of rodent models.

Levy-GN; Rodgers-L; Weber-WW
Chem Res Toxicol 1996 Dec; 9(8):1215-1224
A discussion of the application of animal models to the study of the effects of heredity on the human response to chemicals was presented in this paper. The mouse was regarded as an extensively studied model of the human response. Although certain spontaneous mutations were considered useful to research scientists, these naturally occurring mutations were also considered rare and difficult to find. However, many inbred and congenic strains were based on observed spontaneous mutations. Advantages of inbred strains included the stability of strain characteristics, genetic reliability and homogeneity, and the elimination of genetic confounders. Recombinant inbred strains were viewed as useful for evaluating the linkage between traits and determining chromosomal locations. Congenic inbred strains, generated by backcrossing the offspring generation with the parent generation, were considered especially useful; genetically, they differed only in the locus being studied. Congenic strains of mice, rats, and hamsters were employed in research areas such as carcinogenesis, toxicology, teratogenesis, sensory, growth, aging, and behavior. The creation of double congenic inbred strains for the study of two genetic polymorphisms was also addressed. Recombinant congenic inbred strains involved the separation of the unlinked components of a multigene trait into inbred strains. Exposing animals to mutagens was considered one way to increase the rate of spontaneous, random mutation. By targeting specific genes, their functions in the mammalian system were elucidated. The practice of replacing a normal gene with an inactive gene in transgenic mice, thus generating knockout mice, was also mentioned. Quantitative trait loci mapping was viewed as a suitable approach to determining the number and nature of genes involved in multifactorial traits, as well as chromosome locations, in the mouse and rat. The authors conclude that animal models are extremely helpful in the study of the human response to chemicals.
NIOSH-Publication; NIOSH-Grant; Grants-other; Laboratory-animals; Genetic-factors; Genetics; Chromosome-disorders; Toxic-effects
Pharmacology University of Michigan 6322 Medical Science I Bldg Ann Arbor, MI 48109-0626
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Journal Article
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Other Occupational Concerns; Grants-other
Source Name
Chemical Research in Toxicology
Performing Organization
University of Michigan at Ann Arbor, Ann Arbor, Michigan