SOURCES OF VARIABILITY IN MUTANT FREQUENCY DETERMINATIONS IN DIFFERENT ORGANS OF LACZ PLASMID-BASED TRANSGENIC MICE - EXPERIMENTAL FEATURESAND STATISTICAL-ANALYSIS

Sources of variability that may affect the measurement of mutant frequ encies in lacZ plasmid-based transgenic mice, including rescue-to-resc ue, animal-to-animal (within organ), and organ-to-organ, were studied in the context of some of the experimental features that distinguish t his model From other currently used systems. Statistical analysis of r epealed determinations of DNA from kidney, spleen, liver, lung, and br ain indicated that 350,000 colony-forming units from each of three ani mals should be analyzed per treatment group in order to detect a 50% d ifference in mutant frequencies. Consideration is given to some of the experimental features of the transgenic assay system, including its p ositive selection system, its rescue efficiency, the ability to detect large deletions in the lacZ target genes, the contribution of Escheri chia coil-derived mutations to the spontaneous mutant frequencies obse rved in vivo, and cost effectiveness of mutant frequency determination s. (C) 1997 Wiley-Liss, Inc.