Establishment of immortalized Schwann cells from Sandhoff mice and corrective effect of recombinant human beta-hexosaminidase A on the accumulated GM2 ganglioside.
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.
Ohsawa
Mai
M
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.
Kotani
Masaharu
M
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.
Tajima
Youichi
Y
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.
Tsuji
Daisuke
D
CREST, JST, Kawaguchi, Japan.|Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
Ishibashi
Yasuhiro
Y
CREST, JST, Kawaguchi, Japan.|Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
Kuroki
Aya
A
CREST, JST, Kawaguchi, Japan.|Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
Itoh
Kohji
K
CREST, JST, Kawaguchi, Japan.|Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
Watabe
Kazuhiko
K
CREST, JST, Kawaguchi, Japan.|Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan.
Sango
Kazunori
K
Department of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan.
Yamanaka
Shoji
S
Department of Pathology, School of Medicine, Yokohama City University, Yokohama, Japan.
Sakuraba
Hitoshi
H
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.
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*
D011994:Recombinant Proteins; D001619:beta-N-Acetylhexosaminidases