ENU mutagenesis in the mouse electrophoretic specific-locus test 2. Mutational studies of mature oocytes

Lewis, Susan E.; Barnett, Lois B.; Shelby, Michael D.

doi:10.1016/0165-1110(92)90036-9

Cited by 9 publications

(6 citation statements)

References 22 publications

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“…It is mutagenic in maturing oocytes, as well as in oocytes that have stopped their meiosis in prophase I, both in Drosophila [Zimmering and Thompson, 1984;Zimmering et al, 1989] and mouse [Ehling and Neuhäuser-Klaus, 1988;Lewis et al, 1992]. Although the mutation frequency induced in female germ cells of Drosophila and mouse was much lower than in male germ cells, no attempt has been made previously to determine if the differences in mutation frequency were accompanied by differences in the types of mutations induced.…”

Section: Introductionmentioning

confidence: 92%

“…Although a great number of agents have been tested for mutagenicity in male germ cells, there have been only a few mutagenicity studies in female germ cells. These studies have shown large differences between male and female responses not only with respect to the sensitivity to mutation [Masui and Pedersen, 1975;Zimmering and Thompson, 1984;Ehling and Neuhäuser-Klaus, 1988;Zimmering et al, 1989;Katoh et al, 1990;Sudman and Generoso, 1991;Lewis et al, 1992;Russell and Russell, 1992;Sudman et al, 1992;Tease, 1992], but also in the behavior of the different germ-cells stages [Zimmering and Thompson, 1984;Zimmering et al, 1989;Tease, 1992].…”

Section: Introductionmentioning

confidence: 98%

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O‐ethylthymidine adducts are the most relevant damages for mutation induced by N‐ethyl‐N‐nitrosourea in female germ cells of Drosophila melanogaster

Álvarez¹,

Comendador²,

Sierra³

2002

Environ and Mol Mutagen

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Responses to genotoxic agents vary not only among organisms, test systems, and cellular stages, but also between sexes; little, however, is known about the mutagenic consequences of chemical exposures to female germ cells. In this study, the mutagenicity of N-ethyl-N-nitrosourea (ENU) was analyzed in female germ cells of Drosophila melanogaster using the recessive-lethal test and the vermilion system, which simultaneously generates information on induced mutation frequency and mutation spectrum. ENU was mutagenic in all stages of oogenesis, although there were differences among the stages. In mature and immature oocytes, ENU-induced mutations in the vermilion locus were 43.5% A:T-->G:C transitions, 39.1% A:T-->T:A transversions, 8.7% G:C-->A:T transitions, and 8.7% A:T-->C:G transversions, indicating that the most important premutagenic lesions induced by this chemical are O(4)-ethylthymine and O(2)-ethylthymine. The low frequency of mutation involving O(6)-ethylguanine (i.e., G:C-->A:T transitions) could be a consequence of the repair of these lesions by O(6)-methylguanine DNA methyltransferase. Comparison of these results with those previously obtained in male germ cells stresses the importance of the repair activity of the analyzed cells, because the mutation spectrum in female germ cells was similar to the spectrum obtained with repair-proficient spermatogonial cells and different from repair-deficient postmeiotic cells. The results also indicate that studies with female germ cells could be an alternative to the use of premeiotic male germ cells, especially when the analysis of these cells is difficult or almost impossible and when studies of in vivo DNA repair in premeiotic germ cells are performed.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 98%

O‐ethylthymidine adducts are the most relevant damages for mutation induced by N‐ethyl‐N‐nitrosourea in female germ cells of Drosophila melanogaster

Álvarez¹,

Comendador²,

Sierra³

2002

Environ and Mol Mutagen

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“…The 'Multiple Loci' test has been the most extensively used but other tests such as the 'Spot test' 6 (Russell & Matter, 1980), the comparative analysis of electrochemical changes induced by the mutagen in proteins with an enzymatic activity (Lewis et al, 1991(Lewis et al, , 1992, the 'Dominant Lethals' test (Favor, 1986(Favor, , 1994, and the transgenic mouse strains BigBlueä and Mu-taäMouse have also been used (Ashby, Gorelick & Shelby, 1997). The 'Multiple Loci' test has been the most extensively used but other tests such as the 'Spot test' 6 (Russell & Matter, 1980), the comparative analysis of electrochemical changes induced by the mutagen in proteins with an enzymatic activity (Lewis et al, 1991(Lewis et al, , 1992, the 'Dominant Lethals' test (Favor, 1986(Favor, , 1994, and the transgenic mouse strains BigBlueä and Mu-taäMouse have also been used (Ashby, Gorelick & Shelby, 1997).…”

Section: Enu Is By Far the Most Potent Mutagenmentioning

confidence: 99%

“…Susan Lewis and co-workers (Johnson & Lewis, 1981;Lewis et al, 1991Lewis et al, , 1992 then Marshall et al (1983) and Peters, Ball and Andrews (1986) developed a sort of 'electrophoretic multiple loci test' and in so doing identified many new mutations. Susan Lewis and co-workers (Johnson & Lewis, 1981;Lewis et al, 1991Lewis et al, , 1992 then Marshall et al (1983) and Peters, Ball and Andrews (1986) developed a sort of 'electrophoretic multiple loci test' and in so doing identified many new mutations.…”

Section: The Induction Of New Mutations In Specific Regions Of the Momentioning

confidence: 99%

“…Strain BTBR has been reported as one of the most resistant (Shedlovsky et al, 1993) while FVB appeared rather susceptible (Davis, Woychik & Justice, 1999). DBA/2 is also relatively resistant to the toxic effects of ENU while in strain C57BL/6, a high percentage of males do not recover fertility after treatment (Lewis et al, 1991(Lewis et al, , 1992. DBA/2 is also relatively resistant to the toxic effects of ENU while in strain C57BL/6, a high percentage of males do not recover fertility after treatment (Lewis et al, 1991(Lewis et al, , 1992.…”

Section: The Induction Of New Mutations In Specific Regions Of the Momentioning

confidence: 99%

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Chemical mutagenesis of the mouse genome: an overview

Gu�net

2004

Genetica

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The careful comparison of the phenotypic variations generated by different alleles at a given locus, including of course, those alleles with a deleterious effect, is often an important source of information for the understanding of gene functions. In fact, every time it is possible to match a specific alteration observed at the genomic level with a particular pathology, it is possible to establish a relationship between a gene and its function. When considered from this point of view, the production of new mutations by experimental mutagenesis appears as an alternative to the strategy of in vitro gene invalidation by homologous recombination in embryonic stem (ES) cells, with the advantage that experimental mutagenesis does not require any previous knowledge of the gene structure at the molecular level. Homologous recombination in ES cells is a 'gene driven' approach, in which mutant alleles are produced for those genes that we already know. Experimental mutagenesis, on the contrary, is a 'phenotype driven' approach, in which unknown genes are identified based on phenotypic changes. Also, while homologous recombination in ES cells requires a rather sophisticated technology, mutagenesis is simple to achieve but relies greatly on the efficiency of the mutagenic treatment as well as on the use of an accurate protocol for phenotyping. In this review, we will address a few comments about the different techniques that can be used for the induction of point mutations in the mouse germ line with special emphasis on chemical mutagenesis. We will also discuss the limitations of experimental mutagenesis and the necessity to look for alternative ways for the discovery of new genes and gene functions in the mouse.

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Chemical mutagenesis of the mouse genome: an overview

Guénet

Mutagenesis of the Mouse Genome

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ENU mutagenesis in the mouse electrophoretic specific-locus test 2. Mutational studies of mature oocytes

Cited by 9 publications

References 22 publications

O‐ethylthymidine adducts are the most relevant damages for mutation induced by N‐ethyl‐N‐nitrosourea in female germ cells of Drosophila melanogaster

O‐ethylthymidine adducts are the most relevant damages for mutation induced by N‐ethyl‐N‐nitrosourea in female germ cells of Drosophila melanogaster

Chemical mutagenesis of the mouse genome: an overview

Chemical mutagenesis of the mouse genome: an overview

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