title: Establishment of immortalized Schwann cells from Sandhoff mice and corrective effect of recombinant human beta-hexosaminidase A on the accumulated GM2 ganglioside.
abstract: We have established spontaneously immortalized Schwann cell lines from dorsal root ganglia and peripheral nerves of Sandhoff mice. One of the cell lines exhibited genetically and biochemically distinct features of Sandhoff Schwann cells. The enzyme activities toward 4-methylumbelliferyl N-acetyl-beta-D-glucosamine (beta-hexosaminidases A, B, and S) and 4-methylumbelliferyl N-acetyl-beta-D-glucosamine-6-sulfate (beta-hexosaminidases A and S) were decreased, and GM2 ganglioside accumulated in lysosomes of the cells. Incorporation of recombinant human beta-hexosaminidase isozymes expressed in Chinese hamster ovary cells into the cultured Sandhoff Schwann cells via cation-independent mannose 6-phosphate receptors was found, and the incorporated beta-hexosaminidase A degraded the accumulated GM2 ganglioside. The established Sandhoff Schwann cell line is useful for investigation and development of therapies for Sandhoff disease.
authors.affiliation: CREST, JST, Kawaguchi, Japan.|Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8613, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Ohsawa
authors.affiliation: CREST, JST, Kawaguchi, Japan.|Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8613, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kotani
authors.affiliation: CREST, JST, Kawaguchi, Japan.|Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8613, Japan.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Tajima
authors.affiliation: CREST, JST, Kawaguchi, Japan.|Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsuji
authors.affiliation: CREST, JST, Kawaguchi, Japan.|Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ishibashi
authors.affiliation: CREST, JST, Kawaguchi, Japan.|Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kuroki
authors.affiliation: CREST, JST, Kawaguchi, Japan.|Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Itoh
authors.affiliation: CREST, JST, Kawaguchi, Japan.|Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Watabe
authors.affiliation: Department of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sango
authors.affiliation: Department of Pathology, School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamanaka
authors.affiliation: CREST, JST, Kawaguchi, Japan. sakuraba@rinshoken.or.jp.|Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8613, Japan. sakuraba@rinshoken.or.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakuraba
mesh_terms: D000818:Animals; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts; D020143:Gangliosidoses, GM2 / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D011994:Recombinant Proteins / Q000494:pharmacology*; D012497:Sandhoff Disease / Q000201:enzymology*; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D001619:beta-N-Acetylhexosaminidases / Q000494:pharmacology*
chemical_list: D011994:Recombinant Proteins; D001619:beta-N-Acetylhexosaminidases