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Sensitivity of the ΦX174 am3 allele in relation to the endogenous Hprt gene for detecting mutation in transgenic mice
Author(s) -
Chen James B.,
Dass S. Balachandra,
Burkhart James G.,
Heflich Robert H.
Publication year - 1998
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/(sici)1098-2280(1998)32:3<229::aid-em5>3.0.co;2-0
Subject(s) - allele , genetics , biology , mutation , gene , transgene , genetically modified mouse , microbiology and biotechnology
Transgenic mice have been developed containing multiple, chromosomally integrated copies of the ΦX174 am3 allele that serve as reporters for in vivo mutation at a single A:T basepair. In this study, we examined the relative sensitivity of the am3 transgene for detecting the in vivo mutagenicity of N ‐ethyl‐ N ‐nitrosourea (ENU). Three‐week‐old male ΦX174 mice were treated with 0, 40, and 160 mg/kg of ENU. After 1, 3, 6, and 9 weeks, animals were killed, their spleens removed, and isolated splenocytes were used to measure mutant frequencies (MFs) in both the am3 allele and the endogenous Hprt gene. For animals treated with 40 mg/kg of ENU, the Hprt assay detected an average 22‐fold increase over background, while the am3 MFs averaged threefold above background. With the 160 mg/kg dose, the Hprt assay detected a 54‐fold average increase, while a sixfold average increase above background was found for the transgenic locus. We conclude that the sensitivity of the am3 assay to ENU was compromised by the presence of ex vivo mutations. Adjustment of am3 MFs to exclude these ex vivo mutants could enhance the sensitivity of the assay. Environ. Mol. Mutagen. 32:229–235, 1998 © 1998 Wiley‐Liss, Inc.