Probert Fay, Rice Paul, Scudamore Cheryl L, Wells Sara, Williams Roger, Hough Tertius A, Cox I Jane
†Mary Lyon Centre, MRC Harwell, Oxfordshire OX11 0RD, United Kingdom.
‡Institute of Hepatology, Foundation for Liver Research, 69-75 Chenies Mews, London WC1E 6HX, United Kingdom.
J Proteome Res. 2015 May 1;14(5):2036-45. doi: 10.1021/pr501039k. Epub 2015 Apr 20.
The International Mouse Phenotyping Consortium program has been established to ascribe biological functions to systematically knocked-out (KO) genes by in vivo and ex vivo phenotyping. The plasma clinical chemistry screen includes an assessment of liver, kidney, and bone function and provides a basic lipid profile and histopathology reports on 32 tissues. We report on the inclusion of plasma analysis by proton nuclear magnetic resonance ((1)H NMR) spectroscopy. (1)H NMR spectroscopy data are summarized from 116 running baseline controls with 18 homozygous and 2 heterozygous KO mouse lines along with wild-type controls (typically n = 7 per gender). For the baseline group, the intersample variation of (1)H NMR glucose measurement was 12%, and the (1)H NMR spectroscopy data were influenced by gender and feeding status. There were good correlations between the clinical chemistry and the (1)H NMR spectroscopy measurements for glucose, triglycerides, and HDL cholesterol. Significant differences were observed in two KO lines, Agl (MGI: 1924809) and Bbs5 (MGI: 1919819), by (1)H NMR spectroscopy, clinical chemistry, and histopathology. In a further two KO lines, Elmod1 (MGI: 3583900) and Emc10 (MGI: 1916933), (1)H NMR metabolic differences were observed, but no other ex vivo changes were detected. In the remaining 16 lines, no ex vivo abnormal phenotypes were observed. Plasma (1)H NMR spectroscopy can therefore provide a novel perspective on the function of knocked-out genes.
国际小鼠表型分析联盟计划已经启动，旨在通过体内和体外表型分析来赋予系统性敲除（KO）基因生物学功能。血浆临床化学筛查包括对肝脏、肾脏和骨骼功能的评估，并提供基本的血脂谱以及32种组织的组织病理学报告。我们报告了通过质子核磁共振（（1）H NMR）光谱法进行血浆分析的情况。（1）H NMR光谱数据汇总自116个运行基线对照，其中包括18个纯合和2个杂合KO小鼠品系以及野生型对照（通常每种性别n = 7）。对于基线组，（1）H NMR葡萄糖测量的样本间变异为12%，并且（1）H NMR光谱数据受性别和喂养状态影响。临床化学与（1）H NMR光谱法对葡萄糖、甘油三酯和高密度脂蛋白胆固醇的测量之间存在良好的相关性。通过（1）H NMR光谱法、临床化学和组织病理学观察到，在两个KO品系Agl（MGI: 1924809）和Bbs5（MGI: 1919819）中存在显著差异。在另外两个KO品系Elmod1（MGI: 3583900）和Emc10（MGI: 1916933）中，观察到了（1）H NMR代谢差异，但未检测到其他体外变化。在其余16个品系中，未观察到体外异常表型。因此，血浆（1）H NMR光谱法可为敲除基因的功能提供新的视角。
