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Title: Radiation-induced instability at mouse expanded simple tandem repeat (ESTR) loci
Author: Barber, Ruth Caroline
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2002
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Expanded Simple Tandem Repeat (ESTR) loci provide a useful system to assess the effect of exposure to ionising radiation on the germline of male mice; however, little is known about the mutation mechanism(s) at these loci. Information about mutation processes at these loci may provide important clues concerning the damaging effects of irradiation at the DNA level. A number of approaches have been used to investigate possible mutation mechanisms. No correlation was observed between the levels of meiotic recombination and ESTR mutation rate in the germline of exposed male mice, ruling out the possibility that radiation induced mutation at ESTR loci resulted from an increase in meiotic crossing-over. The analysis of the murine scid mutation on ESTR mutation rate demonstrated that the process of non-homologous end-joining (NHEJ) is important in the stability of ESTR loci in the germline of non-exposed mice, but was unable to ascertain whether the activation of NHEJ could provide a plausible explanation for radiation-induced increases in ESTR mutation rate. A transgenerational study of the descendants of directly exposed male mice provided evidence for a long-term effect of ionising radiation on ESTR stability in the mouse germline. ESTR instability was observed in the germline of the offspring and grandoffspring of the initially irradiated males, with no evidence for a decrease in mutation rate. This analysis also provided additional information about the inheritance of ESTR instability in the mouse germline, demonstrating the possibility that the transmission of instability was epigenetic in nature, and showing that the effect could be observed after exposure to both high- or low-LET sources of irradiation. The data also showed transgenerational effects in three different mouse strains, and that there were no differences in the inheritance of ESTR instability between the male and female germlines. The work presented here provides the basis for a number of new and exciting directions to further analyse radiation-induced mutation at ESTR loci.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available