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Power matters in closing the phenotyping gap 总被引:1,自引:0,他引:1
Meyer CW Elvert R Scherag A Ehrhardt N Gailus-Durner V Fuchs H Schäfer H Hrabé de Angelis M Heldmaier G Klingenspor M 《Die Naturwissenschaften》2007,94(5):401-406
Much of our understanding of physiology and metabolism is derived from investigating mouse mutants and transgenic mice, and
open-access platforms for standardized mouse phenotyping such as the German Mouse Clinic (GMC) are currently viewed as one
powerful tool for identifying novel gene-function relationships. Phenotyping or phenotypic screening involves the comparison of wild-type control mice with their mutant or transgenic littermates. In our study, we explored
the extent to which standardized phenotyping will succeed in detecting biologically relevant phenotypic differences in mice
generated and provided by different collaborators. We analyzed quantitative metabolic data (body mass, energy intake, and
energy metabolized) collected at the GMC under the current workflow, and used them for statistical power considerations. Our
results demonstrate that there is substantial variability in these parameters among lines of wild-type C57BL/6 (B6) mice from
different sources. Given this variable background noise in mice that serve as controls, subtle phenotypes in mutant or transgenic
littermates may be overlooked. Furthermore, a phenotype observed in one cohort of a mutant line may not be reproducible (to
the same extent) in mice coming from a different environment or supplier. In the light of these constraints, we encourage
researchers to incorporate information on intrastrain variability into future study planning, or to perform advanced hierarchical
analyses. Both will ultimately improve the detectability of novel phenotypes by phenotypic screening.
Carola W. Meyer and Ralf Elvert contributed equally to this work. 相似文献
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