SOURCES OF VARIABILITY IN DATA FROM A LACI TRANSGENIC MOUSE MUTATION ASSAY

Experimental features of a transgenic mouse mutation assay based on a lad target transgene from Escherichia coil are considered in detail. S ources 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 fractio ns. The sources include plate-to-plate (within packages), package-to-p ackage (within animals), and animal-to-animal (within study) variabili ty. Data from two laboratories are evaluated, using various statistica l methods to identify excess variability. Results suggest only scatter ed patterns of excess variability, except possibly in those cases wher e genomic DNA from test animals is stored for extended periods (e.g., > 90 days) after isolation from tissues. Further study is encouraged t o examine the validity and implications of this time/storage-related e ffect; (C) 1994 Wiley-Liss, Inc.