¹H NMR metabolic profiling of plasma reveals additional phenotypes in knockout mouse models.

¹H NMR metabolic profiling of plasma reveals additional phenotypes in knockout mouse models.
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血浆的 H NMR 代谢分析揭示了基因敲除小鼠模型中的其他表型。

DOI:
10.1021/pr501039k
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发表时间:
2015
影响因子:
4.4
通讯作者:
Probert F
Probert F
中科院分区:
生物学2区
文献类型:
--
作者:
Probert F

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国际小鼠表型联盟计划已经建立,通过体内和体外表型将生物学功能归因于系统敲除(KO)基因。血浆临床化学筛查包括肝、肾和骨功能的评估,并提供32个组织的基本脂质谱和组织病理学报告。我们报道了质子核磁共振(1H NMR)光谱的等离子体分析。1H NMR数据总结了116个运行基线对照,包括18个纯合子和2个杂合子KO小鼠系以及野生型对照(通常每性别7只)。基线组1h NMR葡萄糖测量样本间变异为12%,1h NMR波谱数据受性别和喂养状况影响。葡萄糖、甘油三酯和高密度脂蛋白胆固醇的临床化学和1h NMR光谱测量之间有很好的相关性。通过1h NMR波谱、临床化学和组织病理学观察,发现两个KO系Agl(MGI: 1924809)和bbs5 (MGI: 1919819)存在显著差异。在另外两个KO系Elmod1(MGI: 3583900)和demc10 (MGI: 1916933)中,观察到1H NMR代谢差异,但未检测到其他离体变化。在其余16个品系中,未观察到体外异常表型。因此,等离子体1h核磁共振光谱可以为敲除基因的功能提供新的视角。
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 (1H NMR) spectroscopy.1H NMR spectroscopy data are summarized from 116 running baseline controls with 18 homozygous and 2 heterozygous KO mouse lines along with wild-type controls (typicallyn= 7 per gender). For the baseline group, the intersample variation of1H NMR glucose measurement was 12%, and the1H NMR spectroscopy data were influenced by gender and feeding status. There were good correlations between the clinical chemistry and the1H NMR spectroscopy measurements for glucose, triglycerides, and HDL cholesterol. Significant differences were observed in two KO lines,Agl(MGI: 1924809) andBbs5(MGI: 1919819), by1H NMR spectroscopy, clinical chemistry, and histopathology. In a further two KO lines,Elmod1(MGI: 3583900) andEmc10(MGI: 1916933),1H 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. Plasma1H NMR spectroscopy can therefore provide a novel perspective on the function of knocked-out genes.
胰岛素过量(功能性胰岛素瘤)和胰岛素缺乏(糖尿病酮症)患者的血液氨基酸水平。
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使用两种标准品测定体积可以通过 NMR 对亚微升样品中的代谢物进行绝对定量和改进的化学计量分析
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发表时间: 2013
影响因子: 7.4
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