Cerebellar degeneration in the Niemann-Pick type C mouse

Chronological morphological changes and topographical distribution of degenerating Purkinje cells were studied in the murine model of Niemann-Pick disease type C (NPC mouse). Loss of Purkinje cells can be detected in the anterior vermis as early as 60 days of age, coinciding with early neurological signs, and progressed to total absence in the entire hemisphere and vermis with exception of nodules. Ultrastructurally, concentric lamellar inclusions were detected in the perikarya of degenerating Purkinje cells as well as in the focally enlarged branching points of their dendrites. Calbindin immunocytochemistry demonstrated dendritic pathology characterized by irregular contour of dendritic trees and decreased number of dendritic spines. Ubiquitin immunoreactivity revealed granular reaction products in the perikarya, dendrites and axons of Purkinje cells. Our studies demonstrated unique pathological features of Purkinje cells that involve perikarya, dendrites and axons in the NPC mouse.