A recombination-based transgenic mouse system for genotoxicity testing

Murti, J R; Schimenti, Kerry J.; Schimenti, John C.

doi:10.1016/0027-5107(94)90268-2

Cited by 25 publications

(8 citation statements)

References 35 publications

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“…Such combinations can also be produced by gene conversion that occurs without crossing-over. Murti and coworkers have shown that not only does gene conversion occur during meiosis in mice, but that it can occur at remarkably high frequencies, in some cases as high as 2% of gametes (81,82). These studies examined meiotic recombination between E. coli lacZ mutations in transgenic mice, and it is possible that gene conversion occurs at a lower frequency in native sequences.…”

Section: The Mhc/hla Complexmentioning

confidence: 94%

Meiotic Recombination Hotspots

Lichten¹,

Goldman²

1995

Annu. Rev. Genet.

337

181

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Meiotic recombination occurs more frequently in some regions of the eukaryotic genome than in others, with variations of several orders of magnitude observed in frequencies of meiotic exchange per unit physical distance. This article reviews what is known abut meiotic recombination hotspots loci, or regions that display a greater than average frequency of meiotic exchange. Hotspots have been most intensively studied in Saccharomyces cerevisiae, which is a major focus of this article. Also reviewed is the current state of knowledge regarding hotspots in other fungi, in maize, in nematodes, in mice, and in humans.

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Section: The Mhc/hla Complexmentioning

confidence: 94%

Meiotic Recombination Hotspots

Lichten¹,

Goldman²

1995

Annu. Rev. Genet.

337

181

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“…Since recombination at direct repeat sequences is rare in somatic cells, the former model analyzes recombination during embryonic development to give rise to a visible phenotype in mature animals, while the latter takes advantage of the fluorescent protein, which increases the detection limits. Directrepeat recombination during spermatogenesis can be measured with other lacZ mice [Murti et al, 1994;Moynahan et al, 1996]. The high frequency of recombination in germ cells allows the detection of recombinant cells by flow cytometry with fluorescent substrates.…”

Section: Other Transgenic Mice For Detection Of Mutations In Vivomentioning

confidence: 99%

Molecular nature of intrachromosomal deletions and base substitutions induced by environmental mutagens

Nohmi

Masumura

2005

Environ and Mol Mutagen

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Cellular DNA is exposed to a variety of exogenous and endogenous mutagens. A complete understanding of the importance of different types of DNA damage requires knowledge of the specific molecular alterations induced by different types of agents in specific target tissues in vivo. The gpt delta transgenic mouse model provides the opportunity to characterize tissue-specific DNA alterations because small and large deletions as well as base substitutions can be analyzed. Here, we summarize the characteristics of intrachromosomal deletions and base substitutions induced by ionizing radiation in liver and spleen, ultraviolet B (UVB) radiation in epidermis, mitomycin C (MMC) in bone marrow, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in colon, and aminophenylnorharman (APNH) in liver of gpt delta mice. Carbon-ion radiation, UVB, and MMC induced large deletions of more than 1 kb. About half of the large deletions occurred between short direct-repeat sequences and the remainder had flush ends, suggesting the involvement of nonhomologous end joining of double-stranded breaks (DSBs) in DNA. UV photoproducts and interstrand crosslinks by MMC may block DNA replication, thereby inducing DSBs. In contrast, PhIP and APNH mainly generated 1 bp deletions in runs of guanine bases. As for base substitutions, UVB and MMC induced G:C-->A:T transitions at dipyrimidine sites and tandem base substitutions at GG sites, respectively. PhIP and APNH induced G:C-->T:A transversions. Translesion DNA synthesis across the lesions, i.e., UV photoproducts, intrastrand crosslinks by MMC, and guanine adducts by the heterocyclic amines, may be involved in the induction of base substitutions. These results indicate the importance of sequence information to elucidate the mechanisms underlying deletions and base substitutions induced in vivo by environmental mutagens.

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“…This is a major advantage compared with in vivo mutagenesis assays which require isolation of DNA from the tissues and subsequent analysis in a second vector system, such as BigBlue® (Köhler et al 1991), Muta™Mouse (Myhr, 1991) and the deletion model of Gossen et al (1995). The COR3 mouse model by Murti et al (1994) and the mouse pink-eye model by Brilliant et al (1991) enable the study of mutations at the cellular level, but are restricted to the study of testis, or patches of eye and coat colour respectively. The main disadvantage of the pKZ1 assays is that screening tissue sections and cell lines for blue staining is labour intensive and the endpoint is visual scoring.…”

Section: Advantages and Disadvantages Of The Pkz1 Assays For Study-inmentioning

confidence: 99%

The PKZ1 Recombination Mutation Assay: A Sensitive Assay for Low Dose Studies

2006

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The majority of mutation studies are performed at high doses of DNA damaging agents due to the insensitivity of most mutation assays. Extrapolation using a linear no-threshold (LNT) dose response model is then used to estimate the extent of possible DNA damage at lower doses. There is increasing evidence to suggest that the LNT model may not be correct at low doses of at least some DNA damaging agents. The pKZ1 in vivo and in vitro recombination assays have proven to be very sensitive for detection of changes in chromosomal inversion in lymphoid tissue in response to low doses of DNA damaging agents. Non-linear dose response curves for chromosomal inversion as an end-point have been identified at low doses of DNA damaging agents using this assay. Here, we review the inversion results obtained to date with the pKZ1 assays and discuss their suitability for low dose studies.

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A recombination-based transgenic mouse system for genotoxicity testing

Cited by 25 publications

References 35 publications

Meiotic Recombination Hotspots

Meiotic Recombination Hotspots

Molecular nature of intrachromosomal deletions and base substitutions induced by environmental mutagens

The PKZ1 Recombination Mutation Assay: A Sensitive Assay for Low Dose Studies

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