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Genetic background determines metabolic phenotypes in the mouse

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Abstract

To evaluate the contribution of genetic background to phenotypic variation, we compared a large range of biochemical and metabolic parameters at different ages of four inbred mice strains, C57BL/6J, 129SvPas, C3HeB/FeJ, and Balb/cByJ. Our results demonstrate that important metabolic, hematologic, and biochemical differences exist between these different inbred strains. Most of these differences are gender independent and are maintained or accentuated throughout life. It is therefore imperative that the genetic background is carefully defined in phenotypic studies. Our results also argue that certain backgrounds are more suited to study a given physiologic phenomenon, as distinct mouse strains have a different propensity to develop particular biochemical, hematologic, and metabolic abnormalities. These genetic differences can furthermore be exploited to identify new genes/proteins that contribute to phenotypic abnormalities. The choice of the genetic background in which to generate and analyze genetically engineered mutant mice is important as it is, together with environmental factors, one of the most important contributors to the variability of phenotypic results.

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Acknowledgments

The authors thank the technicians at the animal facility and the phenotyping platform for their expert technical assistance, Laurent Vasseur for help with statistical analysis, Dr. Thomas Vogt and his colleagues from Merck Research Laboratories for encouragement and stimulating discussions, and Valerie Stengel for logistic support. This work was supported by grants from the French Research Ministry and the Eumorphia (QLRT-2001-00930) and EUMODIC European programs (LSHG-CT-2006-037188).

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Correspondence to Marie-France Champy or Johan Auwerx.

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Champy, MF., Selloum, M., Zeitler, V. et al. Genetic background determines metabolic phenotypes in the mouse. Mamm Genome 19, 318–331 (2008). https://doi.org/10.1007/s00335-008-9107-z

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  • DOI: https://doi.org/10.1007/s00335-008-9107-z

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