Multimodal detection of GM2 and GM3 lipid species in the brain of mucopolysaccharidosis type II mouse by serial imaging mass spectrometry and immunohistochemistry
Multimodal detection of GM2 and GM3 lipid species in the brain of mucopolysaccharidosis type II mouse by serial imaging mass spectrometry and immunohistochemistry
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DOI：
10.1007/s00216-016-0076-x
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发表时间：
2017-02-01
影响因子：
4.3
通讯作者：
Chaurand, Pierre
中科院分区：
文献类型：
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作者：
Dufresne, Martin;Guneysu, Daniel;Chaurand, Pierre
通过在相同组织切片上进行的成像质谱法（IMS）和免疫组织化学（IHC）研究粘多糖样变性II型（亨特氏病）小鼠模型（IdS-KO）。为此，用升华的1，5-二氨基萘包被IdS-KO小鼠脑切片，并通过高空间分辨率IMS（5 μ m）和抗GM 3 IHC在相同组织切片上进行分析，以表征亨特氏病中发现的神经节苷脂单唾液酸化神经节苷脂（GM）沉积物。IMS分析发现，与对照小鼠相比，在IdS-KO小鼠中过表达了两种仅因其脂肪酸残基（硬脂酸或花生酸残基）长度不同的GM 3和GM 2。通过与GM 3标准品相比的组织上精确质量和MS/MS表征GM 3和GM 2。IMS和IHC数据集的重新对齐进一步证实了先前通过提供两个GM 3过度表达的MS信号的IMS图像与抗GM 3 IHC图像的直接相关性检测到的观察到的区域选择性信号。此外，还发现这些区域选择性GM-MS信号在GM 3-IHC染色中具有高度异质性分布。部分沉积物中GM 3和GM 2硬脂酸组分含量较高（r = 0.74），而其他沉积物中GM 3和GM 2花生酸组分含量较高（r = 0.76）。通过高空间分辨率IMS和IHC对亨特氏病小鼠模型进行相同切片分析，可以对GM聚集体的组成进行更深入的分析，同时提供观察到的分子种类的空间分布。
Mucopolysaccharidosis type II (Hunter's disease) mouse model (IdS-KO) was investigated by both imaging mass spectrometry (IMS) and immunohistochemistry (IHC) performed on the same tissue sections. For this purpose, IdS-KO mice brain sections were coated with sublimated 1,5-diaminonaphtalene and analyzed by high spatial resolution IMS (5 mu m) and anti-GM3 IHC on the same tissue sections to characterize the ganglioside monosialated ganglioside (GM) deposits found in Hunter's disease. IMS analysis have found that two species of GM3 and GM2 that are only different due to the length of their fatty acid residue (stearic or arachidic residue) were overexpressed in the IdS-KO mice compared to a control mouse. GM3 and GM2 were characterized by on-tissue exact mass and MS/MS compared to a GM3 standard. Realignment of both IMS and IHC data sets further confirmed the observed regioselective signal previously detected by providing direct correlation of the IMS image for the two GM3 overly expressed MS signals with the anti-GM3 IHC image. Furthermore, these regioselective GM MS signals were also found to have highly heterogeneous distributions within the GM3-IHC staining. Some deposits showed high content in GM3 and GM2 stearic species (r = 0.74) and others had more abundant GM3 and GM2 arachidic species (r = 0.76). Same-section analysis of Hunter's disease mouse model by both high spatial resolution IMS and IHC provides a more in-depth analysis of the composition of the GM aggregates while providing spatial distribution of the observed molecular species.