Sources of variability in data from a lacl transgenic mouse mutation assay

Walter W. Piegorsch, Ann‐Marie C. Lockhart, Barry H. Margolin, Kenneth R. Tindall, Nancy J. Gorelick, Jay M. Short, Gregory J. Carr, Edward D. Thompson, Michael D. Shelby

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Experimental features of a transgenic mouse mutation assay based on a lacl target transgene from Escherichia coli are considered in detail. 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 fractions. The sources include plate‐to‐plate (within packages), package‐to‐package (within animals), and animal‐to‐animal (within study) variability. Data from two laboratories are evaluated, using various statistical methods to identify excess variability. Results suggest only scattered patterns of excess variability, except possibly in those cases where genomic DNA from test animals is stored for extended periods (e.g., > 90 days) after isolation from tissues. Further study is encouraged to examine the validity and implications of this time/storage‐related effect.

Original languageEnglish (US)
Pages (from-to)17-31
Number of pages15
JournalEnvironmental and Molecular Mutagenesis
Volume23
Issue number1
DOIs
StatePublished - 1994
Externally publishedYes

Keywords

  • DNA storage
  • extrabinomial variability
  • hierarchical sampling
  • mutagenicity
  • statistical methods
  • transgene
  • transgenic mouse

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

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  • Cite this

    Piegorsch, W. W., Lockhart, AM. C., Margolin, B. H., Tindall, K. R., Gorelick, N. J., Short, J. M., Carr, G. J., Thompson, E. D., & Shelby, M. D. (1994). Sources of variability in data from a lacl transgenic mouse mutation assay. Environmental and Molecular Mutagenesis, 23(1), 17-31. https://doi.org/10.1002/em.2850230105