Biomedical subjects

M F Festing

Publications and source records attributed to M F Festing.

At least 73 records · Page 4Linked to original sources

PubMed1980

Genetic drift in a stock of laboratory mice.

Genetic drift in an outbred stock of CFLP mice was monitored for 6 years using genetic polymorphism for glucose phosphate isomerase (GPI) and the shape of the mandible as genetic markers. Statistically significant drift was found in both characters. The cause of this drift was not determined, though it could have arisen as a result of genetic sampling during hysterectomy derivation. The use of inbred strains is recommended on theoretical grounds of long-term genetic constancy is needed.

Animals↗

PubMed1980

The choice of animals in toxicological screening: inbred strains and the factorial design of experiment.

Most toxicological screening is currently carried out using genetically variable "outbred" stocks, though the Carcinogenesis Bioassay Programme run by the National Cancer Institute uses a single inbred or F1 hybrid strain of mice and rats. The use of several inbred of F1 hybrid strains in a factorial experiment design would have a number of advantages over either of the current designs. The factorial experiment would need to be no larger, and would therefore not be significantly more expensive, but it would be statistically and biologically more powerful. It should lead to fewer false positive and false negative results, and it offers improved methods of interpreting the results of their significance to man. Eventually, inbred strains will become as widely accepted in toxicology as they are at present in immunology.

Animals↗

PubMed1979

Properties of inbred strains and outbred stocks, with special reference to toxicity testing.

Genetically uniform or isogenic strains (inbred strains and F1 hybrids) have a number of properties that make them valuable in toxicity testing, provided the experimental design can be modified to include more than one such strain. Isogenicity and homozygosity lead to great phenotypic uniformity, high long-term genetic stability, high identifiability, large differences between strains (individuality), and the possibility of setting up daughter colonies genetically identical to the parents. This in turn means that many isogenic strains are internationally distributed, and that considerable background data exist on the characteristics of the common strains. Toxicity testing usually involves the calculation of dose-response curves. Use of phenotypically variable nonisogenic stocks reduces the precision with which such curves can be estimated, without many other benefits. A single isogenic strain may not be satisfactory as it may be resistant to the drug being tested. However, the use of several isogenic strains with a factorial experimental design would overcome this problem, would give high statistical precision, and would provide a better basis for extrapolation to humans than the use of a single stock. Such a design would make it possible to choose a range of strains on the basis of known drug sensitivities, it would be highly repeatable, it would allow comparison of different drugs, and it would show whether the response was genetically determined. The benefits of such an experimental design far outweigh the disadvantages, which are mostly of a practical nature.

Animals↗

PubMed1979

Failure of nude (athymic) rats to become resistant to reinfection with the intestinal coccidian parasite Eimeria nieschulzi or the nematode Nippostrongylus brasiliensis.

The course of each of three successive infections with Eimeria nieschulzi in nude (athymic) rats was the same as the primary infection in nu/+ animals, with the production of more oocysts. This indicates that resistance to reinfection with this parasite is mediated by T lymphocytes but that these cells do not control the duration of the life cycle, since oocyst production was not prolonged in the nu/nu rats. After the three infections with E. nieschulzi, the rats were exposed twice to the intestinal nematode Nippostrongylus brasiliensis, and the nu/nu were completely susceptible even to the second infection. Egg production by both infections in the nu/nu animals was similar and continued at a high plateau level for 28 days before falling to a low level. It appears that the strain of N. brasiliensis used in this study is unable to sustain high egg production for more than 4 weeks in T cell deficient rats.

Animals↗

PubMed1979

Quantitative characters of potential value in studying mutagenesis.

The use of polygenic characters in testing for mutagenicity appears promising. Characters chosen should be easily measured and highly heritable, with a reasonable proportion of the genetic variance being of the additive type, as this implies that polygenic mutations affecting the character would be detectable in the heterozygous state. Changes in such characters may arise as a result of pleiotropic effects of major gene mutations that affect early steps in metabolic pathways.--No single character is likely to be entirely satisfactory; rather a diverse group of biochemical, anatomical and physiological characters, including growth and behavior, should be studied. Mandible shape appears to be particularly promising. The characters may be analysed simultaneously using multivariate techniques. Special attention should be paid to the detection of outliers, which may then be investigated by more classical methods for the presence of mutants. Thus, easily measured, highly heritable polygenic characters may be useful in screening animals for the presence of mutations.

Animals↗

PubMed1979