© 2005 The Japanese Biochemical Society
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Alteration of Brain Type N-Glycans in Neurological Mutant Mouse Brain
1 Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043; 2 Department of Functional Glycomics, Life Science Research Center, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793; and 3 Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki National Research Institutes, Okazaki, Aichi 444-0867
* To whom correspondence should be addressed. Tel: +81-6-6850-5380, Fax: +81-6-6850-5383, E-mail: suhase{at}chem.sci.osaka-u.ac.jp
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 pyridylaminated, 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
1-3(GlcNAcß1-2Man1-6)(GlcNAcß1-4)Manß1-4GlcNAcß1-4(Fuc1-6)GlcNAc (BA-1) to GlcNAcßMan1-3(GlcNAcß1-2Man1-6)(GlcNAcß1-4)Manß1-4GlcNAcß1-4(Fuca1-6)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.
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