Mutations in the F1 generation of mice. 1991

U H Ehling
GSF-Institut für Säugetiergenetik, Neuherberg, Germany.

The occurrence of induced dominant genetic damage can be measured by comparing mutation frequencies in first generation descendants from treated and untreated populations, but for many characters, it is difficult to distinguish between the effects of newly occurring genetic damage and the within-strain variation. This problem has been solved for skeletal abnormalities and for dominant cataract mutations. The skeleton was chosen because it is formed over an extended period of development and is, therefore, presumably subject to modification by gene action expressed during a wide range of time. The direct comparability of the genetic endpoint of mice and men was one aspect which led us to initiate a systematic investigation of the induction of dominant cataracts, an opacity of the lens, in the mouse. Another aspect was that Ehling (1976) developed a concept for the direct estimation of the risk of radiation induced genetic damage to the human population expressed in the first generation, based on the induction of dominant mutations in mammals. Using the direct method we estimated that 20-50 dominant radiation induced mutations would be expected in 19,000 offspring born to parents exposed in Hiroshima and Nagasaki, but only a small proportion of these mutants would have been detected with the techniques used in the population study. The detection of dominant cataract mutations can be combined with the detection of recessive specific locus mutations in mice. The specific locus method consists of mating treated wild-type mice to mice homozygous for seven recessive marker loci and scoring in the first generation offspring for mutations at any of these marked loci. The advantage of a combined investigation of dominant cataract mutations and specific locus mutations is at least three-fold: 1st The number of scorable mutations is increased by a factor of four. 2nd The combined investigation allows the comparison of the mutation frequency of selected and unselected loci. 3rd In the same experiment the frequency of mutations with a dominant and a recessive mode of expression can be compared. The specific locus method was used to investigate the effects of chemicals and radiation on the mutation frequency with respect to the following factors: differential spermatogenic response; changes of the mutation spectrum with different doses of chemicals; comparison of the mutation rates under different treatment conditions; sex and strain differences. Using this method we will demonstrate the possibility to quantify the genetic risk of chemical mutagens. In addition, the per locus ratio of radiation induced dominant to recessive mutations in spermatogonia of the mouse is approximately 1:10.(ABSTRACT TRUNCATED AT 400 WORDS)

UI MeSH Term Description Entries
D008297 Male Males
D008957 Models, Genetic Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment. Genetic Models,Genetic Model,Model, Genetic
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D001847 Bone Diseases Diseases of BONES. Bone Disease,Disease, Bone,Diseases, Bone
D002386 Cataract Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed) Cataract, Membranous,Lens Opacities,Pseudoaphakia,Cataracts,Cataracts, Membranous,Lens Opacity,Membranous Cataract,Membranous Cataracts,Opacities, Lens,Opacity, Lens,Pseudoaphakias
D003433 Crosses, Genetic Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species. Cross, Genetic,Genetic Cross,Genetic Crosses
D005260 Female Females
D005799 Genes, Dominant Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state. Conditions, Dominant Genetic,Dominant Genetic Conditions,Genetic Conditions, Dominant,Condition, Dominant Genetic,Dominant Gene,Dominant Genes,Dominant Genetic Condition,Gene, Dominant,Genetic Condition, Dominant
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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