The twitcher mouse is a mutant affected by a form of leukodystrophy which shows close similarities to human globoid cell (Krabbe&'s) leukodystrophy. Transmission is by an autosomal recessive gene twi. Progressive loss of myelin sheaths from both central and peripheral nervous systems and the presence of inclusion-laden macrophages are characteristic findings. Morphological features of the twitcher have been described by Duchen et al.1. Nerve iso- and allografting have been used to determine the roles of axon and Schwann cell in a number of mouse2 and human3 nerve abnormalities. Schwann cells in a graft proliferate and become associated with regenerating host axons which grow through the graft into the host distal stump. In the twitcher, peripheral nerve axons do not degenerate but are thinner than normal, although there is considerable axonal degeneration in the central nervous system. In 15-day-old mutants, inclusions have been found in Schwann cells associated with apparently normal myelin sheaths. Grafting experiments might show whether the phenotype of this mutant is fully expressed in the Schwann cell, or if axons are also involved. In previous experiments, survival of transplanted Schwann cells was achieved by the use of T cell-suppressed2,3 or nude mice4. We report here that a twitcher nerve transplanted in immunologically unsuppressed animals reproduces all the characteristic features of leukodystrophy and conversely that Schwann cells from unaffected mice can produce normal myelin when associated with twitcher axons.
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Duchen, L. W., Eicher, E. M., Jacobs, J. M., Scaravilli, F. & Teixeira, F. Brain 103, 695–710 (1980).
Aguayo, A. J., Attwell, M., Trecarten, J., Perkins, S. & Bray, G. M. Nature 265, 73–75 (1977).
Aguayo, A. J., Kasarjian, J., Skamene, E., Kongshavn, P. & Bray, G. M. Nature 268, 753–755 (1977).
Dyck, P. K., Lais, A. C. & Low, P. A. Neurology 28, 261–265 (1978).
Schochet, S. S., McCormick, W. F. & Powell, G. F. Acta neuropath. 36, 153–160 (1976).
Yajima, K., Fletcher, T. F. & Suzuki, K. J. neurol. Sci. 33, 179–197 (1977).
Suzuki, K. & Suzuki, Y. Proc. natn. Acad. Sci. U.S.A. 66, 302–309 (1970).
Malone, M. Trans. Am. Soc. Neurochem. 1, 56 (1970).
Kobayashi, T., Scaravilli, F. & Suzuki, K. Proc. 1st Symp. Neurological Mutations Affecting Myelination, Seillac (Abstr.) 257–262 (Elsevier/North-Holland, Amsterdam, 1980).
Romine, J. S., Aguayo, A. J. & Bray, G. M. Brain Res. 98, 601–606 (1975).
Grooth, C.-G. et al. Lancet i, 1260–1264 (1971).
Grooth, C.-G. et al. Transplantn Proc. 11, 1218–1219 (1979).
Guttman, R. D. Transplant Proc. 11, 1622–1625 (1979).
About this article
Cite this article
Scaravilli, F., Jacobs, J. Peripheral nerve grafts in hereditary leukodystrophic mutant mice (twitcher). Nature 290, 56–58 (1981) doi:10.1038/290056a0
Journal of Cellular and Molecular Medicine (2009)
Molecular beacon genotyping for globoid cell leukodystrophy from hair roots in the twitcher mouse and rhesus macaque
Journal of Neuroscience Methods (2007)
Central Nervous System-directed AAV2/5-Mediated Gene Therapy Synergizes with Bone Marrow Transplantation in the Murine Model of Globoid-cell Leukodystrophy
Molecular Therapy (2007)
Developmental Biology (2004)
Microscopy Research and Technique (1995)