title: A comprehensive glycome profiling of Huntington's disease transgenic mice.
abstract: BACKGROUND
  Huntington's disease (HD) is an autosomal, dominantly inherited and progressive neurodegenerative disease, nosologically classified as the presence of intranuclear inclusion bodies and the loss of GABA-containing neurons in the neostriatum and subsequently in the cerebellar cortex. Abnormal processing of neuronal proteins can result in the misfolding of proteins and altered post-translational modification of newly synthesized proteins. Total glycomics, namely, N-glycomics, O-glycomics, and glycosphingolipidomics (GSL-omics) of HD transgenic mice would be a hallmark for central nervous system disorders in order to discover disease specific biomarkers.
  
  
  METHODS
  Glycoblotting method, a high throughput glycomic protocol, and matrix-assisted laser desorption ionization-time of flight/mass spectrometry (MALDI-TOF/MS) were used to study the total glycome expression levels in the brain tissue (3 mice of each sex) and sera (5 mice of each sex) of HD transgenic and control mice. All experiments were performed twice and differences in the expression levels of major glycoforms were compared between HD transgenic and control mice.
  
  
  RESULTS
  We estimated the structure and expression levels of 87 and 58N-glycans in brain tissue and sera, respectively, of HD transgenic and control mice. The present results clearly indicated that the brain glycome and their expression levels are significantly gender specific when compared with those of other tissues and serum. Core-fucosylated and bisecting-GlcNAc types of N-glycans were found in increased levels in the brain tissue HD transgenic mice. Accordingly, core-fucosylated and sialic acid (particularly N-glycolylneuraminic acid, NeuGc) for biantennary type glycans were found in increased amounts in the sera of HD transgenic mice compared to that of control mice. Core 3 type O-glycans were found in increased levels in male and in decreased levels in both the striatum and cortexes of female HD transgenic mice. Furthermore, serum levels of core 1 type O-glycans decreased and were undetected for core 2 type O-glycans for HD transgenic mice. In glycosphingolipids, GD1a in brain tissue and GM2-NeuGc serum levels were found to have increased and decreased, respectively, in HD transgenic mice compared to those of the control group mice.
  
  
  CONCLUSIONS
  Total glycome expression levels are significantly different between HD transgenic and control group mice.
  
  
  CONCLUSIONS
  Glycoblotting combined with MALDI-TOF/MS total glycomics warrants a comprehensive, effective, novel and versatile technique for qualitative and quantitative analysis of total glycome expression levels. Furthermore, glycome-focused studies of both environmentally and genetically rooted neurodegenerative diseases are promising candidates for the discovery of potential disease glyco-biomarkers in the post-genome era.
authors.affiliation: Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, N21 W11, Sapporo 001-0021, Japan; Graduate School of Life Science, Hokkaido University, N21 W11, Sapporo 001-0021, Japan.
authors.forename: Solomon T
authors.initials: ST
authors.lastname: Gizaw
authors.affiliation: Laboratory of Embryonic and Genetic Engineering, Faculty of Advanced Life Science, Hokkaido University, N21 W11, Sapporo 001-0021, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Koda
authors.affiliation: Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, N21 W11, Sapporo 001-0021, Japan; Graduate School of Life Science, Hokkaido University, N21 W11, Sapporo 001-0021, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Amano
authors.affiliation: Laboratory of Embryonic and Genetic Engineering, Faculty of Advanced Life Science, Hokkaido University, N21 W11, Sapporo 001-0021, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kamimura
authors.affiliation: Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, N21 W11, Sapporo 001-0021, Japan; Medicinal Chemistry Pharmaceuticals, Co. Ltd, N21 W12, Sapporo 001-0021, Japan; Graduate School of Life Science, Hokkaido University, N21 W11, Sapporo 001-0021, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Ohashi
authors.affiliation: Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, N21 W11, Sapporo 001-0021, Japan; Medicinal Chemistry Pharmaceuticals, Co. Ltd, N21 W12, Sapporo 001-0021, Japan; Graduate School of Life Science, Hokkaido University, N21 W11, Sapporo 001-0021, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hinou
authors.affiliation: Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, N21 W11, Sapporo 001-0021, Japan; Medicinal Chemistry Pharmaceuticals, Co. Ltd, N21 W12, Sapporo 001-0021, Japan; Graduate School of Life Science, Hokkaido University, N21 W11, Sapporo 001-0021, Japan. Electronic address: shin@sci.hokudai.ac.jp.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005260:Female; D054794:Glycomics; D006028:Glycosphingolipids / Q000378:metabolism; D006816:Huntington Disease / Q000378:metabolism*; D037102:Lectins / Q000032:analysis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D006028:Glycosphingolipids; D037102:Lectins
keywords: Glyco-biomarker; Glycoblotting; Huntington's disease; Total glycomics; Transgenic mouse