Axonal Swellings and Degeneration in Mice Lacking the Major Proteolipid of Myelin

Author:

Griffiths Ian123,Klugmann Matthias123,Anderson Thomas123,Yool Donald123,Thomson Christine123,Schwab Markus H.123,Schneider Armin123,Zimmermann Frank123,McCulloch Mailise123,Nadon Nancy123,Nave Klaus-Armin123

Affiliation:

1. I. Griffiths, T. Anderson, D. Yool, C. Thomson, M. McCulloch, Applied Neurobiology Group, Department of Veterinary Clinical Studies, University of Glasgow, Glasgow G61 1QH, Scotland, UK.

2. M. Klugmann, M. H. Schwab, A. Schneider, F. Zimmerman, K.-A. Nave, Zentrum für Molekulare Biologie (ZMBH), Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.

3. N. Nadon, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City, OK 73104, USA.

Abstract

Glial cells produce myelin and contribute to axonal morphology in the nervous system. Two myelin membrane proteolipids, PLP and DM20, were shown to be essential for the integrity of myelinated axons. In the absence of PLP-DM20, mice assembled compact myelin sheaths but subsequently developed widespread axonal swellings and degeneration, associated predominantly with small-caliber nerve fibers. Similar swellings were absent in dysmyelinated shiverer mice, which lack myelin basic protein (MBP), but recurred in MBP*PLP double mutants. Thus, fiber degeneration, which was probably secondary to impaired axonal transport, could indicate that myelinated axons require local oligodendroglial support.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference22 articles.

1. M. Klugmann, et al., Neuron 18, 59 (1997); D. Boison, W. W. Stoffel, Proc. Natl. Acad. Sci. U.S.A. 91, 11709 (1994); Duncan I. D., Hammang J. P., Trapp B. D., ibid 84, 6287 (1987).

2. F. Seitelberger, S. Urbanits, K.-A. Nave, inNeurodystrophies and Neurolipidoses, H. W. Moser, Ed. (Elsevier Science, Amsterdam, 1996), pp. 559–579; P. Saugier-Veberet al. Nature Genet. 6, 257 (1994); Griffiths I. R., BioEssays 18, 789 (1996).

3. A. Schneider, C. Readhead, I. Griffiths, K.-A. Nave, Proc. Natl. Acad. Sci. U.S.A. 92, 4447 (1995); A. Gow, R. A. Lazzarini, Nature Genet. 13, 422 (1996); Jung M., Sommer I., Schachner M., Nave K.-A., J. Neurosci. 16, 7920 (1996).

4. Mice were fixed by intracardiac perfusion of paraformaldehyde-glutaraldehyde or buffered neutral formalin at various ages between 1 day and 22 months. Tissues were prepared for resin or paraffin embedding. Quantification of axonal spheroids and degeneration was performed at the mid-optic nerve of 4-month-old mice by a point-counting method [M. A. Williams in Practical Methods in Electron Microscopy vol. 6 Quantitative Methods in Biology A. M. Glauert Ed. (North-Holland Amsterdam 1977) pp. 5–84] on electron micrographs at a magnification of ×10 000. About 900 axons per nerve were sampled. Axon diameters in the optic nerve and dorsal funiculus of the cervical spinal cord were measured on the electron micrographs with a digitizer pad and Sumasketch software sampling ∼200 axons per region. The proximal or distal orientation of paranodes relative to the neuronal perikaryon was made on longitudinal sections of optic nerve assuming that most fibers were retinofugally directed.

5. R. L. Friede, A. J. Martinez, Brain Res. 19, 165 (1970); Friede R. L., Miyagishi T., Anat. Rec. 172, 1 (1972).

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