Microbial Status and Genetic Evaluation of Mice and Rats Proceedings of the 1999 US/Japan Conference (2000) / Chapter Skim
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Rat Genetics and Toxicology
Rat Genetics and Toxicology
Pages 97-104
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From page 97... ...
However, most characteristics of toxicologic interest have a polygenic mode of inheritance so the variation is not immediately apparent to most investigators who use only a single stock or strain of rats. A survey of "rat" papers published in Toxicology and Applied Pharmacology in 1979 and 1999 showed that the use of inbred strains has increased from 7% to 31% in the 20-year period.
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From page 98... ...
INTRODUCTION It is now 20 years since ILAR published an excellent set of guidelines on "Laboratory Animal Management: Genetics" (ILAR 1979~. These guidelines described the main types of strains and stocks then available to research workers, which included inbred strains and their derivatives such as congenic strains and recombinant inbred strains, mutants, and "stocks not genetically defined," including outbred stocks.
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From page 99... ...
The results of a study of the first 45 papers published in 1979 and the first 61 papers published in 1999 using the laboratory rat are given in Table 1. The aim was to determine what progress has been made over the last 20 years in encouraging toxicologists to use genetically defined animals and to find out what proportion of papers included more than one strain so that the investigator would have become aware of genetic variation in the observed responses.
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From page 100... ...
Thus, some slight progress has been made in encouraging the use of inbred strains, although whether this rate of progress is acceptable, given the limitations of these outbred stocks, is debatable. None of the papers gave any reasons for choosing the strain used.
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From page 101... ...
Possible experimental designs involve the use of a single inbred strain, a single outbred stock, identical twins, or several isogenic strains but without increasing total numbers. Single inbred strain The first design involves the use of a single inbred strain.
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From page 102... ...
Thus, this design would, in theory, be very good, although in practice, identical twin rats are not available, and it would be inconvenient to use two rats from each of 48 strains. Several isogenic strains, but without increasing total numbers The fourth design is a suitable compromise between the use of a single isogenic strain and the use of twins or 48 isogenic strains.
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From page 103... ...
The use of a multistrain experiment as part of a series of experiments involving the study of toxic mechanisms would alert toxicologists to the importance of genetic variation. Some investigators would then be able to start using modern tools of molecular genetics which would almost certainly lead to a better understanding of toxic mechanisms.
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From page 104... ...
1999. The AH receptor and a novel gene determine acute toxic responses to TCDD: Segregation of the resistant alleles to different rat lines.
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