Hereditary Cerebellar Degenerative Disease (Cerebellar Cortical Abiotrophy) in Rabbits

Abstract

A pair of rabbits gave birth to a set of littermates (F1) with symptoms of early-onset ataxia. Microscopic examination revealed cerebellar degenerative disease in 5 of 6 littermates. Light microscopy was used to compare the thickness of each cerebellar layer in affected animals in contrast to a normal control. Affected animals showed narrowing of the molecular layer of the vermis, reduced density of Purkinje cell dendrites and irregular thickness in their branchlets, and reduced density of granular cells and scattered pyknotic cells in the granular layer. Pyknotic cells were apoptotic granular cells, confirmed by positive staining using the TUNEL method. Electron microscopy confirmed the thinning of the molecular layer seen by light microscopy and also showed a reduced number of parallel fibers, which indicate granular cells axons, and a reduced number of synaptic junctions between Purkinje and granular cells. Purkinje cells had electron-dense, irregularly shaped cytoplasm with irregularly shaped nuclei, and some of these cells had a central chromatolysis-like region. These findings support a diagnosis of cerebellar cortical abiotrophy, a hereditary condition that causes nerve function impairment leading to early-onset progressive degeneration of the cerebellar cortex.

Early Morphological Changes of Hereditary Cerebellar Cortical Abiotrophy in Rabbits

“…Bipolar early granular cells in external granular layer typically extend a radially oriented process toward the Purkinje lamina, while the nucleus and perinuclear organelle move inward within this elongating radial process to reach a final position in the internal granular layer, leaving behind a T-shaped process whose horizontal region becomes the parallel fiber [1,3,13]. Apoptosis of migrating granular cells at early stages can lead to a reduction in the number of parallel fibers and granular cell density in the affected rabbits at advanced stages [16]. However, given that the frequency of apoptosis in migrating cells was low and the cell density of granular cells was normal, granular cells began to degenerate mainly after migration was complete in the affected rabbit.…”

“…To confirm the hereditary form and reproducibility, the same parents of the specific pathogen-free white rabbits (Wbl:JW SPF) from our previous report [16] were mated again to produce F1 rabbits. To confirm gene abnormalities in the female parent, she and another male normal rabbit were mated.…”

“…To confirm gene abnormalities in the female parent, she and another male normal rabbit were mated. Two of six surviving littermates born from the same mated pair were used [16] (Fig. 1, Nos.…”

“…Cerebellar cortical abiotrophy and similar degenerative diseases have been reported to occur in domestic animals [7, 8, 11, 14-16, 18, 19], in some rodents [9,13,17] and in even primates [18], particularly most frequently in dogs [11,15,19], but few reports have addressed the distinct pathogenesis of these disease. In our previous study, affected rabbits showed a slight reduction in number or degeneration of Purkinje cells as well as granular cells with spheroid and vacuolation in the medulla, and a reduced number of the synapses between Purkinje cell spines and parallel fiber terminals at postnatal day (PD) 25-31 [16]. However, because the previous report was a one-point study of rabbits with abiotrophy at advanced stages (around PD 30), we were unable to identify which lesion was primary one, any neuronal cell degeneration, or abnormality of synapse formation.…”

“…We previously investigated the hereditary cerebellar cortical degenerative disease, so-called cerebellar cortical abiotrophy in littermates delivered from a certain pair of rabbits by means of the histopathology, immunohistology and electron microscopy [16]. In abiotrophy, although no abnormalities in the cerebellar components were noted at birth, degeneration often progresses soon after birth or upon reaching adulthood [7,8,18].…”