Neuropathology of gracile axonal dystrophy (GAD) mouse. An animal model of central distal axonopathy in primary sensory neurons.

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.