Metabolic phenotyping of nude and normal (Alpk:ApfCD, C57BL10J) mice

被引:47
作者
McKee, CLG
Wilson, ID
Nicholson, JK
机构
[1] Univ London Imperial Coll Sci Technol & Med, Biomed Sci Div, London SW7 2AZ, England
[2] AstraZeneca, Dept Durg Metab & Pharmacokinet, Macclesfield SKN 4TG, Cheshire, England
关键词
metabotype; molecular phenotype; metabonomics; H-1 NMR spectroscopy; strain difference; gender variation; Nude mouse;
D O I
10.1021/pr050255h
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 H-1 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 strains-the Nude mouse phenotypes being characterized by higher urinary creatinine, guanadinoacetic acid, dimethylamine, alpha-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.
引用
收藏
页码:378 / 384
页数:7
相关论文
共 27 条
[1]   EFFECT OF AGING AND DIET ON PROTON NMR-SPECTRA OF RAT URINE [J].
BELL, JD ;
SADLER, PJ ;
MORRIS, VC ;
LEVANDER, OA .
MAGNETIC RESONANCE IN MEDICINE, 1991, 17 (02) :414-422
[2]   NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition [J].
Bollard, ME ;
Stanley, EG ;
Lindon, JC ;
Nicholson, JK ;
Holmes, E .
NMR IN BIOMEDICINE, 2005, 18 (03) :143-162
[3]   Investigations into biochemical changes due to diurnal variation and estrus cycle in female rats using high-resolution 1H NMR spectroscopy of urine and pattern recognition [J].
Bollard, ME ;
Holmes, E ;
Lindon, JC ;
Mitchell, SC ;
Branstetter, D ;
Zhang, W ;
Nicholson, JK .
ANALYTICAL BIOCHEMISTRY, 2001, 295 (02) :194-202
[4]   Towards a truly integrative biology through the functional genomics of yeast [J].
Delneri, D ;
Brancia, FL ;
Oliver, SG .
CURRENT OPINION IN BIOTECHNOLOGY, 2001, 12 (01) :87-91
[5]   Metabolite profiling by one- and two-dimensional NMR analysis of complex mixtures [J].
Fan, WMT .
PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY, 1996, 28 (pt 2) :161-219
[6]   Metabolite profiling for plant functional genomics [J].
Fiehn, O ;
Kopka, J ;
Dörmann, P ;
Altmann, T ;
Trethewey, RN ;
Willmitzer, L .
NATURE BIOTECHNOLOGY, 2000, 18 (11) :1157-1161
[7]   Directly coupled high-performance liquid chromatography and nuclear magnetic resonance spectroscopic with chemometric studies on metabolic variation in Sprague-Dawley rats [J].
Gavaghan, CL ;
Nicholson, JK ;
Connor, SC ;
Wilson, ID ;
Wright, B ;
Holmes, E .
ANALYTICAL BIOCHEMISTRY, 2001, 291 (02) :245-252
[8]   Physiological variation in metabolic phenotyping and functional genomic studies: use of orthogonal signal correction and PLS-DA [J].
Gavaghan, CL ;
Wilson, ID ;
Nicholson, JK .
FEBS LETTERS, 2002, 530 (1-3) :191-196
[9]   An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences:: application to the C57BL10J and Alpk:ApfCD mouse [J].
Gavaghan, CL ;
Holmes, E ;
Lenz, E ;
Wilson, ID ;
Nicholson, JK .
FEBS LETTERS, 2000, 484 (03) :169-174
[10]   The biochemical profile of rat testicular tissue as measured by magic angle spinning 1H NMR spectroscopy [J].
Griffin, JL ;
Troke, J ;
Walker, LA ;
Shore, RF ;
Lindon, JC ;
Nicholson, JK .
FEBS LETTERS, 2000, 486 (03) :225-229