Spectra of gpt mutations in ethylnitrosourea-treated and untreated transgenic mice

✍ Scribed by K. Masumura; M. Matsui; M. Katoh; N. Horiya; O. Ueda; H. Tanabe; M. Yamada; H. Suzuki; T. Sofuni; T. Nohmi

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 197 KB
• Volume: 34
• Category: Article
• ISSN: 0893-6692
• DOI: 10.1002/(sici)1098-2280(1999)34:1<1::aid-em1>3.0.co;2-p

✦ Synopsis

We have established a new transgenic mouse mutagenicity assay for the efficient detection of point mutations and deletions in vivo (Nohmi et al. [1996] Env. Mol. Mutagen. 28:465-470). In this assay, the gpt gene of Escherichia coli is used as a reporter for the detection of point mutations. Treatment of mice with ethylnitrosourea (ENU, 150 mg/ kg) enhances by several-fold the mutant frequency of gpt in bone marrow. Here, we report the mutation spectra of the gpt gene recovered from bone marrow of ENU-treated and untreated transgenic mice. In the gpt mutants rescued from ENU-treated mice, more than 90% of the mutations were base change mutations; the predominant types were A:T to T:A transversions and G:C to A:T transitions. On the contrary, in the mutants rescued from untreated mice, 54% were base substitutions and the remainders were short deletions and insertions. Among untreated mice, the most frequently observed base substitution was G:C to A:T transitions (7/14 mutants). Three of these occurred at 5Ј-CpG-3Ј sites. Interestingly, the mutation spectra of the gpt gene were different from those of the gpt gene in ENUtreated and untreated E. coli, whereas they were similar to those of the lacZ and lacI genes in ENUtreated and untreated other transgenic mice or cultured mammalian cells. We also report the establishment of homozygous transgenic mice that have transgene EG10 DNA in both chromosome 17 of C57BL/6J mouse. Environ. Mol. Mutagen.