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α1,6-Fucosyltransferase Knockout Mice and Schizophrenia-Like Phenotype

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Sugar Chains

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Abstract

The glycan core fucose is catalyzed by α1,6-fucosyltransferase (Fut8), which transfers a fucose residue to the innermost GlcNAc residue via α1,6-linkage on N-linked glycans (N-glycans) in mammals. N-glycan is always attached to the nitrogen atom of an asparagine (Asn) side chain that is present in the Asn-X-Ser/Thr motif on a protein, where X is any amino acid except proline. The α1,6-fucosylated (core-fucosylated) N-glycan is ubiquitously distributed in all tissues. Interestingly, the unique structure of the core-fucosylated hybrid, one of three major types of N-glycans, is highly expressed in brain tissues, and the expression pattern of N-glycans is altered during brain development. The Fut8-deficient (Fut8−/−) mice exhibit emphysema-like changes in the lungs and severe growth retardation due to dysregulation of the TGF-β1 receptor and the EGF receptor, respectively. To understand the role of core fucosylation in brain tissue, a combination of neurological and behavioral tests for Fut8−/− mice was examined. Fut8−/− mice displayed multiple behavioral abnormalities, such as increased locomotion, decrease in working memory, strenuous hopping behavior, and prepulse inhibition deficiency, which were consistent with a schizophrenia-like phenotype. Here, we summarized the knowledge of the biological functions of core fucosylation, especially its role in brain and neural cells, and discussed possible underlying molecular mechanisms.

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Authors and Affiliations

  1. Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan

    Wei Gu, Tomohiko Fukuda & Jianguo Gu

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  1. Wei Gu
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  2. Tomohiko Fukuda
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  3. Jianguo Gu
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Correspondence to Jianguo Gu .

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Editors and Affiliations

  1. Glycometabolome Team, Systems Glycobiology Research Group, RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama, Japan

    Tadashi Suzuki

  2. Department of Analytical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Kazuaki Ohtsubo

  3. Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama, Japan

    Naoyuki Taniguchi

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Gu, W., Fukuda, T., Gu, J. (2015). α1,6-Fucosyltransferase Knockout Mice and Schizophrenia-Like Phenotype. In: Suzuki, T., Ohtsubo, K., Taniguchi, N. (eds) Sugar Chains. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55381-6_17

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