Shambling (shm) is a neurological mutant mouse of which a mutated gene encodes an axolemmal protein, Caspr (contactin-associated protein). Caspr is a main component of the paranode flanking Nodes of Ranvier in myelinated nerves. In shm mice, paranodal junctions are absent from the paranode of myelinated nerves and the conduction velocity is reduced in the central and peripheral nervous system. Early onset of motor deficits in shm mice advances as mice age so that the aged mice are suffered from severer motor dysfunction and become occasionally immobilized. To clarify such pathophysiological process and assess the disease mechanism of shm mice, here we examined if the cerebellum was affected during development and aging. The cerebellar formation; foliation, layer formation and neuronal differentiation, i.e., Purkinje cells and granule cells was normal in juvenile (P13~17) shm mice. At the adult age (3 months old), however, CD-28K immunohistochemistry revealed that some Purkinje cell (PC) axons had local swellings. At 6 months old, a substantial increase in PC axonal swellings was found and some PCs were disappeared. A loss of PCs became extensively in broad regions of the cerebellum in aged mice. The PC axonal swelling was immunopositive for IP3 receptor, SMI31 (phosphorylated neurofilament, p-NF-H) and SMI32 (non-phosphorylated NF-H). However, not all CD-28K positive PC axonal swellings were immunopositive for either SMI31 or SMI32. PC somata were occasionally strong-immunopositive for SMI32 and, in addition, they were surrounded by hypertrophied SMI32 positive axons in aged mice. EM analysis showed that PC axonal swellings contained ER stacks, clustered mitochondria and autophagosome-like organelles, suggesting that the axonal transport was impaired in shm mice. These altered organelles except ER stacks were present in aged PC somata. Thus, the present finding demonstrated that cytoplasmic alteration of PC axons began with the adult age, worsened in aging and axonal degeneration preceded degeneration of PC somata and cell death, concomitant with advanced neurological phenotypes of shm mice.