Abstract
Animals with spontaneous mutations affecting myelin formation have provided useful information about the genetic and cellular mechanisms regulating normal and abnormal myelination. In this paper we describe a novel murine mutation termed hindshaker (hsh) which is inherited in an automosal recessive manner. Affected mice are characterised by a variable tremor of the hind end which commences at about 2 weeks of age and largely disappears in animals older than 6 weeks. There is hypomyelination affecting predominantly the spinal cord, although the optic nerves and brain are involved to a much lesser degree. The defect of thinly myelinated and naked axons is maximal at 20 days of age and largely resolves with time so that in the adult most axons are myelinated. The myelin structure appears normal and immunostains for the major proteins. Although the distribution of oligodendrocytes in the spinal cord is similar to normal during the period of hypomyelination, there are fewer mature cells. The hsh mutation appears to delay the maturation of oligodenrocytes, particularly in the spinal cord. Additionally, there is a considerable variation in phenotypic expression and in penetrance when the mutation is expressed on different genetic backgrounds, suggesting the hsh locus is subject to the influence of modifying gene(s). Identification of the hsh gene should identify a factor important in the development of oligodendrocytes, particularly those in the spinal cord.
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References
Beechey, C. V. (1993) A new spontaneous neurological mutant. Mouse Genome 91, 114–15.
Bjartmar, C., Hildebrand, C. & Loinder K. (1994) Morphological heterogeneity of rat oligodendrocytes: electron microscopic studies on serial sections. Glia 11, 233–44.
Boison, D. & Stoffel, W. (1994) Distribution of the compacted myelin sheath of axons of the central nervous system in proteolipid protein-deficient mice. Proceedings of the National Academy of Sciences USA 91, 11709–13.
Butt, A. M., Ibrahim, M., Ruge, F. M. & Berry, M. (1995) Biochemical subtypes of oligodendrocyte in the anterior medullary velum of the rat as revealed by the monoclonal antibody Rip. Glia 14, 185–97.
Duncan, I. D. (1987) Abnormalities of myelination of the central nervous system associated with congenital tremor. Journal of Veterinary Internal Medicine 1, 10–23.
Duncan, I. D. (1990) Dissection of the phenotype and genotype of the X-linked myelin mutants. Annals of the New York Academy of Sciences 605, 110–21.
Ebersole, T. A., Chen, Q., Justice, M. J. & Artzt, K. (1996) The quaking gene product necessary in embryogenesis and myelination combines features of RNA binding and signal transduction proteins. Nature Genetics 12, 260–5.
Giese, K. P., Martini, R., Lemke, G., Soriano, P. & Schachner, M. (1992) Mouse P 0, gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons. Cell 71, 565–76.
Griffiths, I. R. (1996) Myelin mutants: model systems to study normal and abnormal myelination. BioEssays 118, 789–97.
Griffiths, I. R., Mitchell, L. S., Mcphilemy, K., Morrison, S., Kyriakides, E. & Barrie, J. A. (1989) Expression of myelin protein genes in Schwann cells. Journal of Neurocytology 18, 345–52.
Griffiths, I. K., Scott, I., Mcculloch, M. C., Barrie, J. A., Mcphilemy, K. & Cattanah, B. M. (1990) Rumpshaker mouse: a new X-linked mutation affecting myelination: evidence for a defect in PLP expression. Journal of Neurocytology 19, 273–83.
Klugmann, M., Schwab, M., PÜHLHOFER, A., Schneider, A., Zimmermann, F., Griffiths, I. R. & Nave, K. (1997) Assembly of CNS myelin in the absence of proteolipid protein. Neuron 18, 59–70.
Knapp, P. E., Skoff, R. P. & Redstone, D. W. (1986) Oligodendroglial cell death in jimpy mice: an explanation for the myelin deficit. Journal of Neuroscience 6, 2813–22.
Knapp, P. E. & Skoff, R. P. (1993) Jimpy mutation affects astrocytes: Lengthening of the cell cycle in vitro. Developmental Neuroscience 15, 31–6.
Kornegay, J. N., Goodwin, M. A. & Spyridakis, L. K. (1987) Hypomyelination in a Weimaraner dog. Acta Neuroyathologica (Berlin) 72, 394–401.
Lawson, H. A., Griffiths, I. R., Montague, P. & Cattanach, B. M. (1996) Hindshaker: a novel myelin mutant shows differential hypomyelination in the CNS. Neuropathology and Applied Neurobiology 22, 144 (Abstract).
Lunn, K. F., Fanarraga, M. L. & Duncan, I. D. (1995) Myelin mutants: New models and new observations. Microscopic Research Techniques 32, 183–203.
Martini, R., Zielasek, J., Toyka, K. V., Giese, K. P. & Schachner, M. (1995) Protein zero (P0-deficient mice show myelin degeneration in peripheral nerves characteristic of inherited human neuropathies. Nature Genetics 11, 281–6.
Mitchell, L. S., Gillespie, C. S., Mcallister, F., Fanarraga, M., Kirkham, D., Kelly, B., Brophy, P. J., Griffiths, I. R., Montague, P. & Kennedy, P. G. E. (1992) Developmental expression of the major myelin protein genes in the CNS of the X-linked hypomyelinating mutant rumpshaker. Journal of Neuroscience Research 33, 205–17.
Nave, K.-A. (1994) Neurological mouse mutants and the genes of myelin. Journal of Neuroscience Research 38, 607–12.
Nave, K.-A. (1996) Myelin-specific genes and their mutations in the mouse. In Glial Cell Development. Basic Principles and Clinical Relevance (edited by Jessen, K. R. and Richardson, W. D.), pp. 141–64. Oxford: Bios.
PERRY, V. H., HUME, D. A. & GORDON, S. (1985) Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience 15, 313–26.
PIDDLESDEN, S. J., LASSMANN, H., ZIMPRICH, F., MORGAN, B. P. & LININGTON, C. (1993) The demyelinating potential of antibodies to myelin oligodendrocyte glycoprotein is related to their ability to fix complement. American Journal of Patholology 143, 555–64.
Remahl, S. & Hildebrand, C. (1990) Relation between axons and oligodendroglial cells during initial myelination. I. The glial unit. Journal of Neurocytoloy 19, 313–28.
Skoff, R. P. (1976) Myelin deficit in the jimpy mouse may be due to cellular abnormalities in astroglia. Nature 264, 560–2.
Sternberger, L. A., Hardy, P. H. J., Cuculis, J. J. & Meyer, H. G. (1970) The unlabelled antibody-enzyme method of immunocytochemistry. Preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. Journal of Histochemistry and Cytochemistry 18, 315–33.
Suzuki, K. & Nagara, H. (1982) Quaking mouse: vacuolar degeneration of spinal roots. Acta Neuropathologica (Berlin) 58, 269–74.
Suzuki, K. & Zagoren, J, C. (1997) Quaking mouse: an ultrastructural study of the peripheral nerves. Journal of Neurocytology 6, 71–84.
Trap, B. D., Itoyam, Y., Sternberger, N. H., Quarles, R. H. & Webster, H. D. (1981) Immunocytochemical localization of P0 protein in Golgi complex membranes and myelin of developing rat Schwann cells. Journal of Cell Biology 90, 1–6.
Trapp, B. D., Moench, T., Pulley, M., Barbosa, E., Tennekoon, G. I. & Griffin, J. W. (1987) Spatial segregation of mRNA encoding myelin-specific proteins. Proceedings of the National Academy of Sciences USA 84, 7773–7.
Williams, M. A. (1977) Stereological techniques. In Practical Methods in Electron Microscopy. Vol. 6. Quantitative Methods in Biology (edited by GLAUERT, A. M.), pp. 5–84. Amsterdam: North Holland.
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King, H., McCulloch, M.C., Barrie, J.A. et al. Hindshaker, a Novel Myelin Mutant Showing Hypomyelination Preferentially Affecting the Spinal Cord. J Neurocytol 26, 557–566 (1997). https://doi.org/10.1023/A:1015486508111
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DOI: https://doi.org/10.1023/A:1015486508111