Untargeted metabolite profiling of murine embryos to reveal metabolic perturbations associated with neural tube closure defects.
Untargeted metabolite profiling of murine embryos to reveal metabolic perturbations associated with neural tube closure defects.
复制标题
鼠类胚胎的未靶向代谢物分析，以揭示与神经管闭合缺陷相关的代谢扰动。
DOI：
10.1002/bdra.23272
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发表时间：
2014-08
影响因子：
--
通讯作者：
Gross, Steven S.
中科院分区：
文献类型：
--
作者：
Hansler, Alex;Chen, Qiuying;Gray, Jason D.;Ross, M. Elizabeth;Finnell, Richard H.;Gross, Steven S.
Neural tube closure defects (NTDs) are among the most common congenital malformation in human, typically presenting in liveborns as spina bifida. At least 240 gene mutations in mouse are known to increase the risk of NTD. There is a growing appreciation that environmental factors significantly contribute to NTD expression, and that NTDs likely arise from complex gene-environment interactions. Because maternal folic acid supplementation reduces human NTD risk in some populations by 60–70%, it is likely that NTD predisposition is often associated with a defect in folate-dependent one-carbon metabolism. A comprehensive, untargeted metabolic survey of NTD-associated changes in embryo metabolism would provide a valuable test of this assumption. We sought to establish a metabolic profiling platform that is capable of broadly assessing metabolic aberrations associated with NTD-promoting gene mutations in early-stage mouse embryos. An LC/MS-based untargeted metabolite profiling platform was employed to broadly identify significant differences in small molecule levels (50 – 1,000 Da) in NTD-affected E9.5 mouse embryos (Lrp6−/−) vs. unaffected (Lrp6+/+) control embryos. Results provide proof-of-principal feasibility for the broad survey of the metabolome of individual E9.5 mouse embryos and identification of metabolic changes associated with NTDs and gene mutations. Levels of 30 different metabolites were altered in association with Lrp6 gene deletion. Some metabolites link to folate-dependent one-carbon transfer reactions, as anticipated, while others await structure elucidation and pathway integration. Whole-Embryo Metabolomics offers the potential to identify metabolic changes in genetically determined NTD-prone embryos.
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影响因子：
7.9
作者：
Ross, M. Elizabeth
通讯作者：
Ross, M. Elizabeth
影响因子：
3.5
作者：
Gray, Jason D.;Nakouzi, Ghunwa;Ross, M. Elizabeth
通讯作者：
Ross, M. Elizabeth
影响因子：
3.9
作者：
SCHIRCH, V;STRONG, WB
通讯作者：
STRONG, WB
DOI：
10.1002/ajmg.c.30057
发表时间：
2005-05-15
影响因子：
3.1
作者：
Mitchell, LE
通讯作者：
Mitchell, LE
影响因子：
3.5
作者：
Juriloff, DM;Harris, MJ
通讯作者：
Harris, MJ