Unfortunately, inbred strains do not stay absolutely genetically constant. Mutations occur, and when they do there is a 1/4 that that they will become fixed. This will change the properties of the strain, although whether it will affect an individual research project depends on the nature of the mutation.
History of genetic drift
Up to the 1950s many geneticists failed to appreciate the importance of mutation in causing genetic change within an inbred strain. Visible mutations occurred occasionally, leading to new substrains, but a study of substrain differentiation of skeletal characteristics in C3H mice showed that many invisible mutations were also occurring, and becoming fixed so that separated substrains gradually drifted apart (Green 1953). Subsequent work from GrÃ¼neberg’s laboratory showed that such substrain differentiation is a continuing process, although there is a strong suspicion that the large substrain differences found in the C3H strain may be due to genetic contamination rather than mutation (McLaren and Tait 1969).
Substrains such as C57BL/6 and C57BL/10 which have been separated since about 1930 do differ genetically. Partly this is due to new mutations, but some is probably due to residual heterozygosity, i.e. the failure of the inbreeding to eliminate all the genetic variation before the substrains were separated. Some biologically important mutations such as the one governing susceptibility to bacterial lipopolysaccharide in C3H mice have also been identified. Substrain variation must not be ignored in research. However, nor should itâ€™s practical importance be overemphasised. Genotype- environment interaction and genetic contamination are probably more important in changing the relative relationships between strains than is substrain differentiation.
Green EL (1953), A skeletal difference between sublines of the C3H strain of mice, Science 117: 81-82
McLaren A, Tait A (1969), Cytoplasmic isocitrate dehydrogenase variation within the C3H inbred strain, Genetical Research 14: 93
Drift and genetic nomenclature
The rules of genetic nomenclature take account of genetic drift.