Untitled

Abstract

As part of a larger literature study on transgenic animals in mutagenicity testing, test results from the transgenic mutagenicity assays (lacI model; commercially available as the Big Blue® mouse, and the lacZ model; commercially available as the Muta™Mouse), were compared with the results on the same substances in the more traditional mouse bone marrow micronucleus test. 39 substances were found which had been tested in the micronucleus assay and in the above transgenic mouse systems. Although, the transgenic animal mutation assay is not directly comparable with the micronucleus test, because different genetic endpoints are examined: chromosome aberration versus gene mutation, the results for the majority of substances were in agreement. Both test systems, the transgenic mouse assay and the mouse bone marrow micronucleus test, have advantages and they complement each other. However, the transgenic animal assay has some distinct advantages over the micronucleus test: it is not restricted to one target organ and detects systemic as well as local mutagenic effects.

Characterisation of MutaTMMouse gt10-lacZ transgene: evidence for in vivo rearrangements

“…However, the Southern blot data suggests that copy number is about the same for all strains. More recently, the copy number for Muta™Mouse has been described as 40 per haploid genome, without reference to how this copy version was derived ( 38 , 39 ). This amount slightly exceeds the averaged estimates by slot blot hybridisation for a cell line (FE1) derived from one of our animals ( 7 ).…”

Genetically altered mice, man and medicine

“…Although these models have yet to be formally accepted into the regulatory testing framework, the US Food and Drug Administration have suggested how several of these models could be used in this context. Similarly, the Organisation for Economic Cooperation and Development (OECD) is considering the benefits of using the lacI BigBlue TM mouse and LacZ Muta®mouse transgenic models for mutagenicity testing (Wahnschaffe et al 2005). The mutagenic target of Muta®mouse is a bacterial LacZ gene, and the target of Big Blue is the LacI repressor gene.…”

The Relevance of Genetically Altered Mouse Models of Human Disease

“…Another example of how the use of GM mice can have a positive impact on animal welfare is the use of reporter mice for mutagenicity (or genotoxicity) testing. The Organisation for Economic Cooperation and Development (OECD) is considering the benefits of using the LacI BigBlue® mouse and LacZ Muta™mouse transgenic models for mutagenicity testing (81). The mutagenic target of Muta™mouse is a bacterial LacZ gene, and the target of Big Blue is the LacI repressor gene.…”

“…The use of such models for mutagenicity testing has the potential to provide a means to screen mutagens which may have escaped detection in simpler assays, such as the mouse spot test and mouse bone-marrow micronucleus test, since it is possible to monitor the ability of mutagens to trigger mutations in more than one type of tissue, without using large numbers of animals (81,82). Indeed, despite differences between the endpoints, tests based on the use of these transgenic models and the mouse spot test or in vivo micronucleus test have similar predictabilities.…”