Analysis Tools
behavior/neurological
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• mice develop progressive motor and behavioral deficit after 3 months of age
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• mice show limb-clasping reflexes at around 6-8 months of age
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• mice show severely impaired motor coordination on the rotarod at 4 months of age, showing shorter staying times on the rod
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• gait disturbance progresses such that mice can hardly move at terminal stage of around 15 months
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nervous system
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• progressive loss of cerebellar Purkinje cells; Purkinje cell loss is first seen in the first cerebellar lobule at about 3 months of age and majority are lost by 12 months of age, remaining only in the 10th cerebellar lobule
• loss of Purkinje cell bodies and dendrites is patterned and selective
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• cells with eosinophilic cytoplasm and condensed nuclei are seen in the granule layer, suggesting apoptosis
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• the perikarya of cerebellar granule cells exhibits accumulation of lipofuscin-like electron-dense material
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• the number of granule cells is the granule layer is decreased
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• scattered PAS+ macrophages/microglia are seen in the molecular layer of the cerebellum
• however, GABAergic interneurons in the molecular layer are similar to wild-type mice
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astrocytosis
(
J:283977
)
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• activated astrocytes are seen in areas of Purkinje cell loss
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• trigeminal nerve shows ganglion cells with inclusion bodies; storage materials consist of many soap-bubble-like inclusions surrounded by membranes
• foamy inclusions are seen in the non-neuronal vascular endothelial cells in the cerebellum
• however, no pathological lesions including neuronal storage are seen in the cerebral cortex, hippocampus, thalamus, amygdala, caudate/putamen and substantia nigra and no signs of demyelination are seen in the central or peripheral nervous system
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• axonal spheroids are evident in the cerebellar granular layers, brain stems, and in the dorsal horn of spinal cords
• spheroids consist of axons filled with membrane-derived concentric or lamellar bodies often containing mitochondria-like structures
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cardiovascular system
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• foamy inclusions are seen in the non-neuronal vascular endothelial cells in the cerebellum
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homeostasis/metabolism
| N |
• no accumulation of glucosylceramide is seen in the brain and liver, even at terminal stage of about 12 months and no major abnormalities in profiles of other lipids are seen
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• activity of glucosylceramidase is lower
• however, activity of GM1-ganglioside beta-galactosidase and beta-hexaminidase is unchanged
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hematopoietic system
| N |
• mice show no signs of hepatosplenomegaly throughout life and spleen shows no changes
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liver/biliary system
| N |
• mice show no signs of hepatosplenomegaly throughout life and liver shows no changes
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reproductive system
| N |
• mice are fertile and testis are normal
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| NOT | Gaucher's disease | DOID:1926 | J:283977 | |
