[Ubiquitin immunoreactivity in the central nervous system of gracile axonal dystrophy (GAD) mouse].

In order to know the relationship of ubiquitin and axonal degeneration in the central nervous system (CNS) of the gracile axonal dystrophy (GAD) mutant mouse, the immunocytochemical study was performed in the spinal cord, medulla oblongata and brain of normal and GAD mice at 4, 9, 18 and 32 weeks of age. The polyclonal antibodies of ubiquitin were used for this study. The results were as follows: Many ubiquitin-positive dot-like structures (DS) were first observed in the gracile nucleus affected primarily with axonal degeneration. They extended to the gracile fasciculus on the dorsal part of spinal cord in accordance with the dying-back type degeneration. The second-order neurons at Clarke's nucleus were also affected slightly later stages and revealed ubiquitin-positive DS along the posterior spinocerebellar tract and the white matter of certain lobes of cerebellum. In 18th week, the transneuronal degeneration started from the distal axonal ends of the primary sensory neurons came up to the some parts of cortical neurons through the secondary neurons in the thalamus. The ubiquitin-positive DS were detected on the ventral surface of the medulla oblongata and increased progressively in number along the corticospinal (pyramidal) tract of spinal cord which consists of the descending fibers derived from the cortical neurons. These findings suggest that abnormal proteins in the degenerating axons were ubiquitinated rapidly before they accumulated in the preterminal axons whose neuron stems are far away from the place, and that GAD mouse would be a useful animal model to know the mechanism(s) of the naturally occurring transneuronal degeneration from the distal axonal ends of both ascending sensory neurons and descending pyramidal neurons in the CNS.