Chapter 22 Timing of neuronal replacement in cerebellar degenerative ataxia of Purkinje cell type

The “Purkinje cell degeneration” (pcd) mutant is characterized by a genetically determined loss of virtually all Purkinje cells between 17 and 45 days of age. The mutation is recessive; homozygous females (pcd/pcd) are fertile, whereas homozygous males are sterile. In solid cerebellar grafts, transplanted in pcd mutants, donor Purkinje cells survive and differentiate. The extent, pattern, and timing of degeneration, along with a comparative analysis of data from other cerebellar mutants characterized by Purkinje cell deficits, support the notion that all of these changes are most likely secondary to the loss of Purkinje cells. Thus, it appears that in pcd mutants as well, transneuronal losses proceed at a slower rate than losses that are under a primary genetic influence. To prevent transneuronal cell loss, the transplantation of Purkinje cells should optimally be carried out before such losses have occurred. However, the fate of donor Purkinje cells, grafted at the onset of host Purkinje cell degeneration, remains undefined.