1. ¹CREST, JST, Kawaguchi, Japan
2. ²Department 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
3. ³Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan
4. ⁴Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan
5. ⁵Department of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan
6. ⁶Department of Pathology, School of Medicine, Yokohama City University, Yokohama, Japan

Correspondence: Hitoshi Sakuraba, 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. Fax: +81-3-38236008. E-mail: sakuraba@rinshoken.or.jp

Received 2 June 2005; Accepted 11 July 2005; Published online 23 September 2005.

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--D-glucosamine (-hexosaminidases A, B, and S) and 4-methylumbelliferyl N-acetyl--D-glucosamine-6-sulfate (-hexosaminidases A and S) were decreased, and GM2 ganglioside accumulated in lysosomes of the cells. Incorporation of recombinant human -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 -hexosaminidase A degraded the accumulated GM2 ganglioside. The established Sandhoff Schwann cell line is useful for investigation and development of therapies for Sandhoff disease.