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Article

Metabolic Phenotyping of Nude and Normal (Alpk:ApfCD, C57BL10J) Mice

Claire L. Gavaghan McKee,^†^§ Ian D. Wilson,^‡ and Jeremy K. Nicholson*^†

Biological Chemistry, Biomedical Sciences Division, Imperial College London, Sir Alexander Fleming Building, South Kensington, London, SW7 2AZ, United Kingdom and AstraZeneca, Department of Drug Metabolism and Pharmacokinetics, Alderley Park, Macclesfield, Cheshire, SKN 4TG, United Kingdom

J. Proteome Res., 2006, 5 (2), pp 378–384

DOI: 10.1021/pr050255h

Publication Date (Web): January 19, 2006

†

Imperial College London.

Current address: Claire L. Gavaghan McKee, Computational Toxicology, Safety Assessment, AstraZeneca R &D Mölndal, S431 83, Mölndal, Sweden.

‡

AstraZeneca.

To whom correspondence should be addressed. Tel: +44 (0)20 7594 3195. E-mail: j.nicholson@imperial.ac.uk.

Abstract

Mice provide a range of important models of human disease. As part of a broad program of metabolic phenotyping (metabotyping) the effects of gender and strain upon urinary metabolite composition and variation have been investigated using ¹H NMR spectroscopy and chemometrics in the Alpk:ApfCD, C57BL10J and the “Nude mouse”. By using Principal Components Analysis (PCA) and Soft Independent Modeling by Class Analogy (SIMCA), characteristic metabotypes for each strain were produced for both male and female animals. In all three strains, female urinary metabolic profiles were characterized by higher lactate, trimethylamine-N-oxide and lower trimethylamine concentrations relative to males. Both male and female Nude mice were phenotypically distinct from the Alpk:ApfCD and C57BL10J strainsthe Nude mouse phenotypes being characterized by higher urinary creatinine, guanadinoacetic acid, dimethylamine, α-hydroxy-N-valeric acid and taurine levels and lower hippurate, citrate, creatine and succinate concentrations relative to those excreted by the two phenotypically normal mouse strains. These data show that Nude mice exhibit a wide variety of metabolic differences across a much wider range of pathways than has previously been thought, with potentially important considerations for studies that use the Nude mouse as a mouse model.