Clinical signs of ataxia were noted in 3 male rats from a shipment of 50. Initial data suggested that the ataxia was primarily due to a spontaneous, progressive Purkinje cell (PC) degeneration. The defect is hereditary, appearing in the second generation of inbreeding affected rats. The breeding colony has remained free of murine pathogens including """"""""rat parvovirus other"""""""". Purkinje cell degeneration in humans has been associated with hereditary cerebellar ataxia, alcohol intoxication, certain neoplasias, and aging. While PC degeneration has been induced in rats, a spontaneous rat model of the disease is not available. We propose a series of experiments to identify the temporal and spatial features of PC degeneration in these affected rats and correlate our findings with known human disease states.
Our specific aims are to: 1) identify the spatial distribution of degenerating PC's in the cerebellum at different postnatal ages; 2) determine if PC degeneration is localized to specific subpopulations of PC's; 3) survey other areas of the CNS for neuronal degeneration; 4) determine if degeneration of PC's results in alteration in the organization of spinocerebellar afferent systems; and 5) determine if significant differences exist between normal and affected rats in organs outside the CNS.
