Transgenic rodents are valuable models for investigation of genotoxicity of chemicals
in vivo. We have developed
gpt delta transgenic mice (C57BL/6J background) and rats (Sprague-Dawley, SD), which have the ability to identify both point mutations by the
gpt assay [6-thioguanine (6-TG) selection] and certain types of deletions by the Spi
- (Spi, sensitive to P2 interference) assay. Recently, the
gpt delta SD rat was backcrossed with the Fisher 344 (F344) rat to establish an
gpt delta F344 rat. The average spontaneous
gpt mutation frequencies (MFs) are about 4.5×10
6 in both SD and F344
gpt delta rats as well as in
gpt delta mice. The G:C to A:T transitions at 5'-CpG-3'sites and G:C to T:A transversions are the predominant spontaneous
gpt mutations in rats and mice. However, there is one false mutation (
e.g. A:T to T:A at position 299) in the rats. The base substitution may have arisen when the lambda EG10 transgene was introduced into the genome of the SD rat during transgenesis. In the Spi
- assay, 1-bp deletions in repetitive sequences are predominantly observed in both mice and rats. Possible mechanisms underlying the spontaneous mutations in
gpt delta rodents are discussed.
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