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- W2076547880 abstract "The establishment in recent years of transgenic shuttle vector-based mutagenicity assays has provided improved systems for analysis of mutagenic and carcinogenic processes. Results in the mouse have stimulated the development of an alternative species suitable for mutations analysis and have increased our understanding of the existing models. A previously described shuttle vector (λLIZ), based on a lacl target gene, was constructed in this laboratory for the study of mutagenesis in transgenic mice and in cultured cell lines. The shuttle vector allows for several options in its recovery from the host genome and in mutant identification. Of the 9 transgenic lineages that were generated with the λLIZ vector, one was chosen for use in a standardized and mutagenicity assay (Big Blue®, mouse lineage A1). Characterization of this lineage included copy-number determination, chromosomal localization of transgene integration and analysis of copy-number stability. As part of the validation process, the standardized color-screening assay has been tested in the mouse, both for spontaneous mutant frequencies and with a variety of model mutagenic compounds, and has been shown to identify most major classes of mutations as evidenced by mutant spectra data. A discussion of the relative sensitivity of the shuttle vector to each of these classes is included. These studies have now been extended to the generation of transgenic rats containing the same shuttle vector for cross-species analysis. Spontaneous mutant frequencies in two transgenic rat lineages were measured in liver and in germ cells. Preliminary data suggest that spontaneous mutant frequencies in somatic tissue are lower in rats than in mice, a result consistent with historical observations of DNA damage and repair in these two species. Also under evaluation are alternative selectable systems for mutant identification, and hybrid animals obtained from mating λLIZ transgenics with genetically engineered mice processing an inactivated tumor suppressor gene. It is expected that each of these widely varying endeavors will continue, not only in furthering our understanding of the role transgenic systems should play in human risk assessment, but in illuminating the mechanisms of mutation in general." @default.
- W2076547880 created "2016-06-24" @default.
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- W2076547880 date "1994-06-01" @default.
- W2076547880 modified "2023-10-07" @default.
- W2076547880 title "The use of shuttle vectors for mutation analysis in transgenic mice and rats" @default.
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- W2076547880 doi "https://doi.org/10.1016/0027-5107(94)90257-7" @default.
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