Gavaghan McKee Claire L, Wilson Ian D, Nicholson Jeremy K
Biological Chemistry, Biomedical Sciences Division, Imperial College London, Sir Alexander Fleming Building, South Kensington, London, SW7 2AZ, United Kingdom.
J Proteome Res. 2006 Feb;5(2):378-84. doi: 10.1021/pr050255h.
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 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.
小鼠提供了一系列重要的人类疾病模型。作为广泛的代谢表型分析（代谢分型）计划的一部分，已使用1H核磁共振光谱和化学计量学方法，在Alpk:ApfCD、C57BL10J和“裸鼠”中研究了性别和品系对尿液代谢物组成及变化的影响。通过主成分分析（PCA）和类模型软独立建模（SIMCA），分别生成了雄性和雌性动物各品系的特征代谢型。在所有三个品系中，与雄性相比，雌性尿液代谢谱的特征在于乳酸、氧化三甲胺浓度较高，而三甲胺浓度较低。雄性和雌性裸鼠在表型上均与Alpk:ApfCD和C57BL10J品系不同——相对于两种表型正常的小鼠品系所排泄的水平，裸鼠的表型特征是尿液中肌酐、胍基乙酸、二甲胺、α-羟基-N-戊酸和牛磺酸水平较高，而马尿酸盐、柠檬酸盐、肌酸和琥珀酸盐浓度较低。这些数据表明，裸鼠在比之前认为的更广泛的途径中表现出各种各样的代谢差异，这对于将裸鼠用作小鼠模型的研究具有潜在的重要考量。
