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The Journal of Neuroscience, July 15, 1999, 19(14):6058-6067

Loss of Distal Axons and Sensory Merkel Cells and Features Indicative of Muscle Denervation in Hindlimbs of P0-Deficient Mice

Regula Frei^{1, 3}, Sandra Mötzing¹, Ilka Kinkelin², Melitta Schachner⁴, Martin Koltzenburg¹, and Rudolf Martini^{1, 3}

Departments of ¹ Neurology and ² Dermatology, University of Würzburg, D-97080 Würzburg, Germany, ³ Department of Neurobiology, Swiss Federal Institute of Technology, CH-8093 Zürich, Switzerland, and ⁴ Zentrum für Molekulare Neurobiologie, University of Hamburg, D-20246 Hamburg, Germany

Mice lacking the major Schwann cell myelin component P0 show a severe dysmyelination with pathological features reminiscent of the Déjérine-Sottas syndrome in humans. Previous morphological and electrophysiological studies on these mice did not only demonstrate a compromised myelination and myelin maintenance, but were suggestive of an impairment of axons as well. Here, we studied the axonal pathology in P0-deficient mice by quantitative electron microscopy. In addition, we investigated epidermal receptor end organs by immunocytochemistry and muscle pathology by histochemistry.

In proximal sections of facial and femoral nerves, axon calibers were significantly reduced, whereas the number of myelin-competent axons was not diminished in 5- and 17-month-old P0-deficient mice. However, in distal branches of the femoral and sciatic nerve (digital nerves innervating the skin of the first toe) the numbers of myelin-competent axons were reduced by 70% in 6-month-old P0-deficient mice. Immunolabeling of foot pads revealed a corresponding loss of Merkel cells by 75%, suggesting that survival of these cells is dependent on the presence or maintenance of their innervating myelinated axons. In addition, quadriceps and gastrocnemius muscles showed pathological features indicative of denervation and axonal sprouting. These findings demonstrate that loss of an important myelin component can initiate degenerative mechanisms not only in the Schwann cell but also in the distal portions of myelinated axons, leading to the degeneration of specialized receptor end organs and impairment of muscle innervation.

Key words: hereditary neuropathies; animal models; axonopathy; axonal degeneration; Schwann cell; myelin

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19146058-10$05.00/0

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