The spontaneous mutation tippy causes Purkinje cell defects including abnormal dendrite formation and Purkinje cell degeneration. Homozygotes can be identified by 10 days of age by their smaller body size and difficulty in righting themselves. They can become hyperactive, cannot stand or walk without falling over, and most die by 20 to 25 days of age. Only 25% of Purkinje cells display normal dendritic architecture. Most have abnormal dendritic branching, often having no clear secondary or tertiary dendritic branches. The Purkinje cells have many more spines located along the proximal dendritic shaft and the cell soma than are found in controls. Dendritic branches lack the normal self-avoidance and instead have meandering arbors, which overlap in their coverage, and dendritic spines are malformed, with thin, elongated filopodia. Aberrant Purkinje cell morphology is found throughout all lobules and across the vermis. At 18 days of age torpedos can be found at the initial Purkinje cell axon, and Purkinje cell degeneration is found, primarily in the anterior lobe and the banks of the secondary fissure, with damage in all compartments of the Purkinje neuron. There are more dystrophic axons in the cerebellar and vestibular nuclei than there are those undergoing advanced degeneration, and no vacuoles are observed in the Purkinje cell layer between 16 and 21 days of age. No Purkinje cell degeneration was found in the inferior olivary complex. Foliation and tri-laminar organization of the cerebellum are normal, but the cerebellum is smaller than normal. Granule, stellate, basket, golgi, Lugaro and unipolar brush border cells appear normal and correctly positioned, but there is upreglation of GFAP in Bergmann glia and astroglial cells of the granule layer, white matter and deep nuclei. (Shih et al., 2015 and Lane and Bronson, 1995.)
