Sources of variability in data from a positive selection lacZ transgenic mouse mutation assay: An interlaboratory study

Walter W. Piegorsch, Ann C. Lockhart, Gregory J. Carr, Barry H. Margolin, Terry Brooks, George R. Douglas, Ute M. Liegibel, Takayoshi Suzuki, Véronique Thybaud, Joost H.M. Van Delft, Nancy J. Gorelick

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Experimental features of a positive selection transgenic mouse mutation assay based on a λlacZ transgene are considered in detail, with emphasis on results using germ cells as the target tissue. Sources of variability in the experimental protocol that can affect the statistical nature of the observations are examined, with the goal of identifying sources of excess variation in the observed mutant frequencies. The sources include plate-to-plate (within packages), package-to-package (within animals), and animal-to-animal variability. Data from five laboratories are evaluated in detail. Results suggest only scattered patterns of excess variability below the animal-to-animal level, but, generally, significant excess variability at the animal-to-animal level. Using source of variability analyses to guide the choice of statistical methods, control-vs.-treatment comparisons are performed for assessing the male germ cell mutagenicity of ethylnitrosourea (ENU), isopropyl methanesulfonate (iPMS), and methyl methanesulfonate (MMS). Results on male germ cell mutagenesis of ethyl methanesulfonate (EMS) and methylnitrosourea (MNU) are also reported.

Original languageEnglish (US)
Pages (from-to)249-289
Number of pages41
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume388
Issue number2-3
DOIs
StatePublished - Feb 1997
Externally publishedYes

Keywords

  • Ethylnitrosourea
  • Extra-binomial variability
  • Hierarchical sampling
  • Isopropyl methanesulfonate
  • Methyl methanesulfonate
  • Mutagenicity
  • Positive selection assay
  • Statistical method
  • Transgene
  • Transgenic mouse

ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis

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    Piegorsch, W. W., Lockhart, A. C., Carr, G. J., Margolin, B. H., Brooks, T., Douglas, G. R., Liegibel, U. M., Suzuki, T., Thybaud, V., Van Delft, J. H. M., & Gorelick, N. J. (1997). Sources of variability in data from a positive selection lacZ transgenic mouse mutation assay: An interlaboratory study. Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 388(2-3), 249-289. https://doi.org/10.1016/S1383-5718(96)00123-4