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-β-D-glucosamine (β-hexosaminidases A, B, and S) and 4-methylumbelliferyl N-acetyl-β-D-glucosamine-6-sulfate (β-hexosaminidases A and S) were decreased, and GM2 ganglioside accumulated in lysosomes of the cells. Incorporation of recombinant human β-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 β-hexosaminidase A degraded the accumulated GM2 ganglioside. The established Sandhoff Schwann cell line is useful for investigation and development of therapies for Sandhoff disease.
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Acknowledgement
We wish to thank Dr. Richard L. Proia (Section on Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health) for providing us with the Sandhoff mice. This work was partly supported by grants from CREST, JST, the Tokyo Metropolitan Government, the Japan Society for the Promotion of Science, the Ministry of Education, Science, Sports and Culture, and the Ministry of Health, Labor and Welfare of Japan.
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Ohsawa, M., Kotani, M., Tajima, Y. et al. Establishment of immortalized Schwann cells from Sandhoff mice and corrective effect of recombinant human β-hexosaminidase A on the accumulated GM2 ganglioside. J Hum Genet 50, 460–467 (2005). https://doi.org/10.1007/s10038-005-0278-0
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DOI: https://doi.org/10.1007/s10038-005-0278-0
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