Acta Neuropathologica

, Volume 79, Issue 3, pp 294–299 | Cite as

Neuropathology of gracile axonal dystrophy (GAD) mouse

An animal model of central distal axonopathy in primary sensory neurons
  • M. Mukoyama
  • K. Yamazaki
  • T. Kikuchi
  • T. Tomita
Regular Papers


A new neurological mutant mouse shows a gracile axonal dystrophy (GAD). The degenerative lesion develops by postnatal day 80, first appearing in the most rostral portion of the gracile fascicles. This lesion then extends caudally to involve the entire gracile fascicles. Many axonal swellings (dystrophies) also appear in the degenerative lesions in proportion to their severity. The clinical findings develop in keeping with these pathological changes, and are characterized by tremor, ataxia and difficulty in moving the hind limbs. These start around day 80, and progress gradually to death about day 150. The lumbar dorsal roots, their spinal root ganglia and peripheral nerves are normal. Electron microscopic study shows dystrophic axons packed with neurofilaments, mitochondria and tubulovesicular structures. These may reflect some stagnation of axonal transport. The distribution of the lesions suggest that the GAD mouse has a central distal axonopathy involving primary sensory neurons of the lumbar dorsal root ganglia.

Key words

Gracile axonal dystrophy (GAD) mouse Gracile fascicles Neuroaxonal dystrophy Central distal axonopathy 


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  1. 1.
    Baumgartner G, Gawel MJ, Kaeser HE, Pallis CA, Rose FC, Schaumburg HH, Thomas PK, Wadia NH (1979) Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan. J Neurol Neurosurg Psychiatry 42:1073–1083Google Scholar
  2. 2.
    Behan WMH, Maia M (1974) Strümpell's familial spastic paraplegia: genetics and neuropathology. J Neurol Neurosurg Psychiatry 37:8–20Google Scholar
  3. 3.
    Blakemore WF, Cavanagh JB (1969) “Neuroaxonal dystrophy” occurring in an experimental “dying back” process in the rat. Brain 92:789–804Google Scholar
  4. 4.
    Cowen P, Olmstead EV (1963) Infantile neuroaxonal dystrophy. J Neuropathol Exp Neurol 22:175–236Google Scholar
  5. 5.
    Fujisawa K (1967) An unique type of axonal alternation (so-called axonal dystrophy) as seen in Goll's nucleus of 277 cases of controls. A contribution to the pathology of aging process. Acta Neuropathol (Berl) 8:255–275Google Scholar
  6. 6.
    Krinke G, Schaumburg HH, Spencer PS, Thomann P, Hess R (1979) Clioquinol and 2,5-hexanedione induce different types of distal axonopathy in the dog. Acta Neuropathol (Berl) 47:213–221Google Scholar
  7. 7.
    Pentschew A, Schwarz K (1962) Systemic axonal dystrophy in vitamin E deficient adult rats. With implication in human neuropathology. Acta Neuropathol (Berl) 1:313–334Google Scholar
  8. 8.
    Sacks OW, Aguilar MJ, Brown WJ (1966) Hallervorden-Spatz disease: its pathogenesis and place among the axonal dystrophies. Acta Neuropathol (Berl) 6:167–174Google Scholar
  9. 9.
    Spencer PS, Schaumburg HH (1977) Ultrastructural studies of the dying-back process. III The evolution of experimental peripheral giant axonal degeneration. J Neuropathol Exp Neurol 36:276–298Google Scholar
  10. 10.
    Spencer PS, Schaumburg HH (1977) Ultrastructural studies of the dying-back process. IV Differential vulnerability of PNS and CNS fibers in experimental central-peripheral distal axonopathies. J Neuropathol Exp Neurol 36:300–320Google Scholar
  11. 11.
    Sung JH (1964) Neuroaxonal dystrophy in mucoviscidosis. J Neuropathol Exp Neurol 23:567–583Google Scholar
  12. 12.
    Tateishi J, Ikeda H, Saito A, Kuroda S, Otsuki S (1972) Myeloneuropathy in dogs induced by iodoxyquinoline. Neurology 22:702–709Google Scholar
  13. 13.
    Wujek JR, Lasek RJ (1983) Correlation of axonal regeneration and slow component b in two branches of a single axon. J Neurosci 3:243–251Google Scholar
  14. 14.
    Yamazaki K, Wakasugi N, Tomita T, Kikuchi T, Mukoyama M, Ando K (1988) Gracile axonal dystrophy (GAD), a new neurological mutant in the mouse. Proc Soc Exp Biol Med 187:209–215Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • M. Mukoyama
    • 1
    • 2
  • K. Yamazaki
    • 2
    • 3
    • 4
  • T. Kikuchi
    • 2
  • T. Tomita
    • 3
  1. 1.Chubu National HospitalOhbu, AichiJapan
  2. 2.National Institute of NeuroscienceNCNPTokyoJapan
  3. 3.Faculty of AgricultureNagoya UniversityNagoyaJapan
  4. 4.Tsukuba Research LaboratoriesEisai Co. Ltd.IbarakiJapan

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