ABSTRACT
Neurodegenerative human diseases are caused by nerve cell death and anatomical changes in some brain regions. Molecular genetic studies of Drosophila showed that this organism can serve as a valuable test-system for conserved mechanisms underlying human nervous system disorders. Analysis of brain functions is possible when the mutants with disturbed functions are available. In this study, we have developed a unique collection of Drosophila melanogaster mutants with morphological and neurodegenerative changes in brain structure, which were induced by chemical mutagens.
Subject(s)
Brain/pathology , Drosophila melanogaster/genetics , Genes, Insect/drug effects , Mutagens/toxicity , Mutation , Animals , Brain/drug effects , Disease Models, Animal , Drosophila melanogaster/drug effects , Ethyl Methanesulfonate/toxicity , Ethylnitrosourea/toxicity , Female , Male , Nerve DegenerationABSTRACT
In a series of Drosophila mutants with changes in the brain structure, some characters (reduced life span, behavioral changes, and neuronal loss in various brain regions) resemble symptoms observed in human patients with neurodegenerative diseases. In addition, similar specific phenotypes shared by different species suggest that common mechanisms underlie degeneration of their nerve cell. This study reports the results of a genetic analysis of new X-chromosome mutants with neurodegenerative changes in brain structure, which were induced by chemical mutagenesis. According to complementation test, all mutants were divided into three complementation groups, in which the life span and dynamics of neurodegenerative changes were studied. The life span of Drosophila melanogaster flies was found to depend on the state of their nervous system.
Subject(s)
Drosophila melanogaster/genetics , Ethyl Methanesulfonate/toxicity , Ethylnitrosourea/toxicity , Mutation , X Chromosome/genetics , Animals , Brain/drug effects , Brain/pathology , Chromosome Mapping , Drosophila melanogaster/drug effects , Female , Genes, Insect/drug effects , Longevity/genetics , Male , Mutagens/toxicity , Nerve Degeneration/chemically induced , Nerve Degeneration/genetics , Nerve Degeneration/pathologyABSTRACT
Under the influence of ethyl methanesulfonate the series of both morphological and structural mutants with different types of brain changes has been obtained in Drosophila melanogaster Oregon R strain. In the future, this collection of mutants will be used in the investigations of genetic control of brain degeneration and possible ways of brain regeneration.
Subject(s)
Brain/cytology , Drosophila melanogaster/drug effects , Ethyl Methanesulfonate/pharmacology , Mutagens/pharmacology , Animals , Brain/drug effects , Drosophila melanogaster/cytology , Drosophila melanogaster/genetics , Female , Male , Mutation , X Chromosome/drug effectsABSTRACT
Molecular genetic mechanisms of the white mutations induced by mitomycin C, N-ethyl-N-nitrosourea, and ethidium bromide were studied. Genomic DNA of the original strain and mutants obtained was tested by Southern blot hybridization. The presence of mobile genetic elements was shown to be characteristic of the white locus of the original strain. Mutations of the white gene obtained mainly resulted from excision of DNA sequences involving mobile genetic elements and insertion of unidentified 5-6-kbp DNA fragments.
Subject(s)
Chromosome Mapping , Drosophila melanogaster/drug effects , Mitomycin/toxicity , Mutagenesis, Insertional , Mutagens/toxicity , Animals , Blotting, Southern , DNA Transposable Elements , Drosophila melanogaster/genetics , Ethidium/toxicity , Ethylnitrosourea/toxicity , GenomeABSTRACT
The spontaneous and X-ray-induced mutation rates and spectrums were estimated in laboratory strains and natural populations of Drosophila melanogaster from the Chernobyl meltdown area. Laboratory strains Oregon R and y2w alpha 4 were stable. In all natural populations, the spontaneous mutation rate was an order of magnitude higher (10(-3)) than in laboratory strains. Irradiation at a total dose of 3000 R was shown to induce genetic instability in the stable laboratory strain y2w alpha 4 and to increase the mutation rate and spectrum range in the unstable natural population P1. A high level of genetic instability was observed both in the first and second generations. Genetic analysis by means of classical genetic and molecular methods was performed; in crosses, a collection of spontaneous and induced mutants was used. The molecular genetic nature of mutations at the white and cut loci was analyzed by Southern blot-hybridization. Mutations at the white locus were shown to result both from transposition and recombination events; cut mutations were caused by deletions.
