Mouse functional genomics requires standardization of mouse handling and housing conditions
The study of mouse models is crucial for the functional annotation of the human genome. The recent improvements in mouse genetics now moved the bottleneck in mouse functional genomics from the generation of mutant mice lines to the phenotypic analysis of these mice lines. Simple, validated, and reproducible phenotyping tests are a prerequisite to improving this phenotyping bottleneck. We analyzed here the impact of simple variations in animal handling and housing procedures, such as cage density, diet, gender, length of fasting, as well as site (retro-orbital vs. tail), timing, and anesthesia used during venipuncture, on biochemical, hematological, and metabolic/endocrine parameters in adult C57BL/6J mice. Our results, which show that minor changes in procedures can profoundly affect biological variables, underscore the importance of establishing uniform and validated animal procedures to improve reproducibility of mouse phenotypic data.
KeywordsCorticosterone Hematological Parameter Blood Parameter Amylase Level Free Fatty Acid Level
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
We thank animal facility technicians for expert technical assistance. This work was supported by grants of CNRS, INSERM, Hôpitaux Universitaires de Strasbourg, Reseau National en Genomique of the French Research Ministry, EU (Eumorphia program; QLRT-2001-00930), and NIH (1-P01-DK59820-01).
Ahima, RS, Prabakaran, D, Flier, JS 1998Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. Implications for energy homeostasis and neuroendocrine functionJ Clin Invest10110201027PubMedGoogle Scholar Boden, G, Chen, X, Mozzoli, M, Ryan, I 1996Effect of fasting on serum leptin in normal human subjectsJ Clin Endocrinol Metab8134193423CrossRefPubMedGoogle Scholar Chowdhury, P, Nishikawa, M, Blevins, GW,Jr, Rayford, PL 2000Response of rat exocrine pancreas to high-fat and high-carbohydrate dietsProc Soc Exp Biol Med223310315CrossRefPubMedGoogle Scholar Dale, JC, Burritt, MF, Zinsmeister, AR 2002Diurnal variation of serum iron, iron-binding capacity, transferrin saturation, and ferritin levelsAm J Clin Pathol117802808CrossRefPubMedGoogle Scholar Johnson, PE, Lukaski, HC, Bowman, TD 1987Effects of level and saturation of fat and iron level and type in the diet on iron absorption and utilization by the ratJ Nutr117501507PubMedGoogle Scholar Kinlaw, WB, Schwartz, HL, Oppenheimer, JH 1985Decreased serum triiodothyronine in starving rats is due primarily to diminished thyroidal secretion of thyroxineJ Clin. Invest7512381241PubMedGoogle Scholar Krotkiewski, M 2002Thyroid hormones in the pathogenesis and treatment of obesityEur J Pharmacol4408598CrossRefPubMedGoogle Scholar Métais, P 1988Biochimie clinique SimepParisGoogle Scholar Nadeau, JH, Balling, R, Barsh, G, Beier, D, Brown, SD, et al. 2001Sequence interpretationFunctional annotation of mouse genome sequences. Science29112511255Google Scholar Nobrega, MA, Pennacchio, LA 2004Comparative genomic analysis as a tool for biological discoveryJ Phvsiol5543139CrossRefGoogle Scholar O’Brien, T, Woychik, R 2003Our small relativeNat Genet3334CrossRefPubMedGoogle Scholar Perez, C, Canal, JR, Dominguez, E, Campillo, JE, Guillen, M, et al. 1997Individual housing influences certain biochemical parameters in the ratLab Anim31357361PubMedGoogle Scholar Riley, JH 1992Clinical pathology: preanalytical variation in preclinical safety assessment studies—effect on predictive value of analyte testsToxicol Pathol20490500PubMedGoogle Scholar Saladin, R, Vos, P, Guerre–Millo, M, Leturque, A, Girard, J, et al. 1995Transient increase in obese gene expression after food intake or insulin administrationNature377527529CrossRefPubMedGoogle Scholar Schnell, MA, Hardy, C, Hawley, M, Propert, KJ, Wilson, JM 2002Effect of blood collection technique in mice on clinical pathology parametersHum Gene Ther13155161CrossRefPubMedGoogle Scholar Skalicky, M, Narath, E, Viidik, A 2001Housing conditions influence the survival and body composition of ageing ratsExp Gerontol36159170CrossRefPubMedGoogle Scholar Tabata, H, Kitamura, T, Nagamatsu, N 1998Comparison of effects of restraint, cage transportation, anesthesia and repeated bleeding on plasma glucose levels between mice and ratsLab Anim32143148PubMedGoogle Scholar Zambrowicz, BP, Sands, AT 2003Knockouts model the 100 best-selling drugs—will they model the next 100?Nat Rev Drug Discov23851CrossRefPubMedGoogle Scholar