Spontaneous mutation in Big Blue® mice from fetus to old age: Tissue-specific time courses of mutation frequency but similar mutation types

2004 ◽  
Vol 43 (2) ◽  
pp. 110-120 ◽  
Author(s):  
Kathleen A. Hill ◽  
Victoria L. Buettner ◽  
Asanga Halangoda ◽  
Makoto Kunishige ◽  
Stephen R. Moore ◽  
...  
Keyword(s):  
Old Age ◽  
Mutation Frequency ◽  
Spontaneous Mutation ◽  
Specific Time ◽  
Tissue Specific ◽  
Time Courses

Tissue-specific time courses of spontaneous mutation frequency and deviations in mutation pattern are observed in middle to late adulthood in Big Blue mice

2005 ◽  
Vol 45 (5) ◽  
pp. 442-454 ◽  
Author(s):  
Kathleen A. Hill ◽  
Asanga Halangoda ◽  
Petra W. Heinmoeller ◽  
Kelly Gonzalez ◽  
Chaniga Chitaphan ◽  
...  
Keyword(s):  
Mutation Frequency ◽  
Spontaneous Mutation ◽  
Specific Time ◽  
Late Adulthood ◽  
Tissue Specific ◽  
Mutation Pattern ◽  
Time Courses ◽  
Spontaneous Mutation Frequency

scholarly journals SPONTANEOUS UNSTABLE UNC-22 IV MUTATIONS IN C. ELEGANS VAR. BERGERAC

Genetics ◽  
1984 ◽  
Vol 108 (4) ◽  
pp. 859-877
Author(s):  
D G Moerman ◽  
R H Waterston
Keyword(s):  
Mutation Frequency ◽  
Spontaneous Mutation ◽  
Phenotypic Effect ◽  
C Elegans ◽  
High Mutation Frequency ◽  
Mutator Activity ◽  
Discrete Site ◽  
Unstable Mutations ◽  
Spontaneous Mutation Frequency ◽  
Forward Mutation

ABSTRACT This paper describes a mutator system in the nematode Caenorhabditis elegans var. Bergerac for the gene unc-22. Of nine C. elegans and two C. briggsae strains tested only the Bergerac BO strain yielded mutant animals at a high frequency and the unc-22 IV gene is a preferred mutational target. The forward spontaneous mutation frequency at the unc-22 locus in Bergerac BO is about 1 × 10-4, and most of these spontaneous unc-22 mutations revert at frequencies between 2 × 10-3 and 2 × 10-4. Both the forward mutation frequency and the reversion frequency are sensitive to genetic background. Spontaneous unc-22 mutations derived in a Bergerac background and placed in a primarily Bristol background revert at frequencies of <10-6. When reintroduced into a Bergerac/Bristol hybrid background the mutations once again become unstable. The mutator activity could not be localized to a discrete site in the Bergerac genome. Nor did mutator activity require the Bergerac unc-22 gene as a target since the Bristol unc-22 homolog placed in a Bergerac background also showed high mutation frequency. Intragenic mapping of two spontaneous unc-22 alleles, st136 and st137, place both mutations in the central region of the known unc-22 map. However, these mutations probably recombine with one another, suggesting that the unstable mutations can occur in more than one site in unc-22. Examination of the phenotypic effect of these mutations on muscle structure indicates that they are less severe in their effect than a known amber allele. We suggest that this mutator system is polygenic and dispersed over the nematode genome and could represent activity of the transposable element Tc1.

scholarly journals Increased Mutation Frequency in Redox-Impaired Escherichia coli Due to RelA- and RpoS-Mediated Repression of DNA Repair

2010 ◽  
Vol 76 (16) ◽  
pp. 5463-5470 ◽  
Author(s):  
Amarjeet Singh ◽  
Anis Karimpour-Fard ◽  
Ryan T. Gill
Keyword(s):  
Escherichia Coli ◽  
Dna Repair ◽  
Mutation Frequency ◽  
Spontaneous Mutation ◽  
Regulatory Gene ◽  
Stringent Response ◽  
Anaerobic Growth ◽  
E Coli ◽  
Direct Measurements ◽  
Order Of Magnitude

ABSTRACT Balancing of reducing equivalents is a fundamental issue in bacterial metabolism and metabolic engineering. Mutations in the key metabolic genes ldhA and pflB of Escherichia coli are known to stall anaerobic growth and fermentation due to a buildup of intracellular NADH. We observed that the rate of spontaneous mutation in E. coli BW25113 (ΔldhA ΔpflB) was an order of magnitude higher than that in wild-type (WT) E. coli BW25113. We hypothesized that the increased mutation frequency was due to an increased NADH/NAD+ ratio in this strain. Using several redox-impaired strains of E. coli and different redox conditions, we confirmed a significant correlation (P < 0.01) between intracellular-NADH/NAD+ ratio and mutation frequency. To identify the genetic basis for this relationship, whole-genome transcriptional profiles were compared between BW25113 WT and BW25113 (ΔldhA ΔpflB). This analysis revealed that the genes involved in DNA repair were expressed at significantly lower levels in BW25113 (ΔldhA ΔpflB). Direct measurements of the extent of DNA repair in BW25113 (ΔldhA ΔpflB) subjected to UV exposure confirmed that DNA repair was inhibited. To identify a direct link between DNA repair and intracellular-redox ratio, the stringent-response-regulatory gene relA and the global-stress-response-regulatory gene rpoS were deleted. In both cases, the mutation frequencies were restored to BW25113 WT levels.

Disruption of Xpg increases spontaneous mutation frequency, particularly A:T to C:G transversion

2001 ◽  
Vol 487 (3-4) ◽  
pp. 127-135 ◽  
Author(s):  
Naoko Shiomi ◽  
Emiko Hayashi ◽  
Shun-ichi Sasanuma ◽  
Kazuei Mita ◽  
Tadahiro Shiomi
Keyword(s):  
Mutation Frequency ◽  
Spontaneous Mutation ◽  
Spontaneous Mutation Frequency

scholarly journals The mutagenicity of amino acid analogues inCoprinus lagopus

1974 ◽  
Vol 23 (1) ◽  
pp. 47-61 ◽  
Author(s):  
Philippa J. Talmud ◽  
D. Lewis
Keyword(s):  
Amino Acid ◽  
Mutation Frequency ◽  
Spontaneous Mutation ◽  
Base Change ◽  
Response Curves ◽  
Amino Acid Analogues ◽  
Single Base Change ◽  
Protein Incorporation ◽  
Dose Dependent ◽  
Spontaneous Mutation Frequency

SummaryThe amino acid analoguesp-fluorophenylalanine (PFP) and ethionine (ETH) are strongly mutagenic inCoprinus lagopus. The most pronounced effect was found with suppressor mutations of themet-1locus. PFP, at a concentration of 2·4 × 10−4M, increased the mutation frequency 500 fold and ETH, at a concentration of 2·4 × 10−3M, 30 fold over the spontaneous mutation frequency. From the spectrum of suppressors of themet-1locus and the dominant revertants of thead-82locus, induced by analogue treatments, it was concluded that both analogues induce single base-change mutations. The dose response curves follow a sigmoid plot, revealing that within a certain range of analogue concentrations, muta-genesis is strongly dose dependent.Using analogue resistant mutants, it has been shown that PFP mutagenesis is a function of its incorporation into protein. However, ETH mutagenesis is independent of protein incorporation but can be correlated with the degree of ethylation of nucleic acids. The synergistic effect PFP and ETH supports the evidence of the different mutagenic actions of the two analogues.

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