Alteration of brain type N-glycans in neurological mutant mouse brain
Alteration of brain type N-glycans in neurological mutant mouse brain
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DOI：
10.1093/jb/mvi125
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发表时间：
2005-09-01
影响因子：
2.7
通讯作者：
Hase, S
中科院分区：
文献类型：
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作者：
Nakakita, S;Natsuka, S;Hase, S
我们先前已经检测到两种脑特异性和发育依赖性N-聚糖[H.清水湾Ochiai，K. Ikenaka，K. Mikoshiba和S. Hase（1993）J.Biochem.114，334-338]。在本研究中，我们试图分析在神经系统突变小鼠中检测到的特异性N-聚糖。将从3周龄神经学突变小鼠（jimpy、staggerer和shiverer）获得的大脑和小脑中的N-聚糖与从正常小鼠获得的N-聚糖进行比较。通过肼解-N-乙酰化从大脑和小脑中释放的N-聚糖是吡啶氨基，并且由此获得的N-聚糖的吡啶氨基衍生物通过阴离子交换色谱分离成中性和五个酸性部分。将每个级分中的PA-N-聚糖与通过反相HPLC从正常小鼠获得的PA-N-聚糖进行比较，并获得以下结果。两种脑型N-聚糖的比例，Man α 1-3（wGlcNAc β 1-2Man α 1-6）（GlcNAc β 1-4GlcNAc β 1-4（Fuc α 1-6）GlcNac）（BA-1）至GlcNAc β Man α 1-3（GlcNAc β 1-2Man α 1-6）（GlcNAc β 1-4）Man β 1-4GlcNAc β 1-4（Fucal-6）GlcNAc（BA-2）在交错小鼠中高于其他突变小鼠和正常小鼠。Sia-Gal-BA-2、三触角N-聚糖和二分双触角N-聚糖在颤抖和蹒跚小鼠的小脑中发现，但在正常或jimpy小鼠中没有发现。高甘露糖型N-聚糖在突变小鼠脑中没有改变。与正常小鼠小脑相比，jimpy小鼠小脑中的双唾液酸双触角N-聚糖和双唾液酸岩藻糖双触角N-聚糖的含量较低，而shiverer小鼠小脑中的含量较高。成功鉴定了突变特异性N-聚糖的一些改变，表明N-聚糖生物合成途径组分的表达在神经学突变中受到特异性影响。
We have previously detected two brain-specific and development-dependent N-glycans [H. Shimizu, K. Ochiai, K. Ikenaka, K. Mikoshiba, and S. Hase (1993) J. Biochem. 114, 334-338]. In the present study we attempted to analyze specific N-glycans detected in neurological mutant mice. N-glycans in cerebrum and cerebellum obtained from 3-week-old neurological mutant mice (jimpy, staggerer, and shiverer) were compared with those obtained from normal mice. N-glycans liberated from the cerebrum and cerebellum by hydrazinolysis-N-acetylation were pyridylamino, and pyridylamino derivatives of N-glycans thus obtained were separated into neutral and five acidic fractions by anion exchange chromatography. PA-N-glycans in each fraction were compared with those obtained from normal mice by reversed-phase HPLC, and the following results were obtained. The ratio of the two brain-type N-glycans, Man alpha 1-3(wGlcNAc beta 1-2Man alpha 1-6)(GlcNAc beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNac)(BA-1) to GlcNAc beta Man alpha 1-3(GlcNAc beta 1-2Man alpha 1-6)(GlcNAc beta 1-4)Man beta 1-4GlcNAc beta 1-4(Fucal-6)GlcNAc (BA-2), was higher in staggerer mice than other mutant mice and normal mice. Sia-Gal-BA-2, triantennary N-glycans, and bisected biantennary N-glycans were found in the cerebellum of shiverer and staggerer mice but not in normal or jimpy mice. High-mannose type N-glycans were not altered in mutant mice brains. The amounts of disialylbiantennary N-glycans and disialylfucosylbiantennary N-glycans were lower in jimpy mouse cerebellum than in normal mouse cerebellum, but were higher in shiverer mouse. Some alterations of N-glycans specific to mutations were successfully identified, suggesting that expression of component(s) of the N-glycan biosynthetic pathway was specifically affected in neurological mutations.