Spectra of gpt mutations in ethylnitrosourea-treated and untreated transgenic mice.
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 5'-CpG-3' sites. Interestingly, the mutation spectra of the gpt gene were different from those of the gpt gene in ENU-treated and untreated E.coli, whereas they were similar to those of the lacZ and lacI genes in ENU-treated and untreated other transgenic mice or cultured mammalian cells. We also report the establishment of homozygous transgenic mice that have transgene lambdaEG10 DNA in both chromosome 17 of C57BL/6J mouse.
Masumura
K
K
Division of Genetics and Mutagenesis, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan.
Matsui
M
M
Katoh
M
M
Horiya
N
N
Ueda
O
O
Tanabe
H
H
Yamada
M
M
Suzuki
H
H
Sofuni
T
T
Nohmi
T
T
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D010582:Bacteriophage lambda / Q000235:genetics; D001483:Base Sequence; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D029968:Escherichia coli Proteins; D005038:Ethylnitrosourea / Q000633:toxicity*; D005260:Female; D006720:Homozygote; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D010430:Pentosyltransferases; D017354:Point Mutation; D011506:Proteins
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D009153:Mutagens; D011506:Proteins; D010430:Pentosyltransferases; C071962:Gpt protein, E coli; D005038:Ethylnitrosourea