Functional analysis of the chondroitin 6-sulfotransferase gene in relation to lymphocyte subpopulations, brain development, and oversulfated chondroitin sulfates

Kenji Uchimura, Kenji Kadomatsu, Hitoshi Nishimura, Hisako Muramatsu, Eishin Nakamura, Nobuyuki Kurosawa, Osami Habuchi, Fathy M. El-Fasakhany, Yasunobu Yoshikai, Takashi Muramatsu

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    Abstract

    Chondroitin 6-sulfotransferase (C6ST) catalyzes the transfer of sulfate to position 6 of the N-acetylgalactosamine residue of chondroitin. To obtain direct evidence regarding the function of C6ST and its product, chondroitin 6-sulfate, in vivo, we isolated the mouse C6ST gene (C6st) and generated mice deficient in this gene (C6st -/-) by embryonic stem cell technology. C6st -/- mice were born at approximately the expected frequency and were viable through adulthood. In the spleen of C6st -/- mice, the level of chondroitin 6-sulfate became almost undetectable. Analyses of these knockout mice provided insights into the biosynthesis of oversulfated chondroitin sulfates in mice; chondroitin sulfate D in the brain of null mice and the cartilage and telencephalon of null embryos disappeared, whereas the chondroitin sulfate E level in the spleen and brain of the null mice was unchanged. Despite the disappearance of chondroitin sulfate D structure, brain development was normal in the C6st -/- mice. Further analysis revealed that the number of CD62L +CD44 low T lymphocytes corresponding to naive T lymphocytes in the spleen of 5-6-week-old C6st -/- mice was significantly decreased, whereas those in other secondary lymphoid organs were unchanged. This finding suggested that chondroitin 6-sulfate plays a role in the maintenance of naive T lymphocytes in the spleen of young mice.

    Original languageEnglish
    Pages (from-to)1443-1450
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume277
    Issue number2
    DOIs
    Publication statusPublished - Jan 11 2002

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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  • Cite this

    Uchimura, K., Kadomatsu, K., Nishimura, H., Muramatsu, H., Nakamura, E., Kurosawa, N., Habuchi, O., El-Fasakhany, F. M., Yoshikai, Y., & Muramatsu, T. (2002). Functional analysis of the chondroitin 6-sulfotransferase gene in relation to lymphocyte subpopulations, brain development, and oversulfated chondroitin sulfates. Journal of Biological Chemistry, 277(2), 1443-1450. https://doi.org/10.1074/jbc.M104719200