Phenotypes Associated with This Genotype

Genotype
MGI:6444206

• Allelic Composition: Psap^tm2.1Juma/Psap^tm2.1Juma
• Genetic Background: involves: 129 * C57BL/6J * FVB/N

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:283977 )

• mice develop progressive motor and behavioral deficit after 3 months of age

limb grasping ( J:283977 )

• mice show limb-clasping reflexes at around 6-8 months of age

tremors ( J:283977 )

• tremors progress over time

impaired coordination ( J:283977 )

• mice show severely impaired motor coordination on the rotarod at 4 months of age, showing shorter staying times on the rod

abnormal gait ( J:283977 )

• gait disturbance progresses such that mice can hardly move at terminal stage of around 15 months

nervous system

Purkinje cell degeneration ( J:283977 )

• 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

abnormal cerebellar granule layer morphology ( J:283977 )

• cells with eosinophilic cytoplasm and condensed nuclei are seen in the granule layer, suggesting apoptosis

abnormal cerebellar granule cell morphology ( J:283977 )

• the perikarya of cerebellar granule cells exhibits accumulation of lipofuscin-like electron-dense material

decreased cerebellar granule cell number ( J:283977 )

• the number of granule cells is the granule layer is decreased

abnormal cerebellar molecular layer ( J:283977 )

• 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

astrocytosis ( J:283977 )

• activated astrocytes are seen in areas of Purkinje cell loss

nervous system inclusion bodies ( J:283977 )

• 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

axonal spheroids ( J:283977 )

• 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

cardiovascular system

abnormal vascular endothelial cell morphology ( J:283977 )

• foamy inclusions are seen in the non-neuronal vascular endothelial cells in the cerebellum

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:283977 )

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

abnormal enzyme/coenzyme level ( J:283977 )

• activity of glucosylceramidase is lower

• however, activity of GM1-ganglioside beta-galactosidase and beta-hexaminidase is unchanged

hematopoietic system

hematopoietic system phenotype ( J:283977 )

N • mice show no signs of hepatosplenomegaly throughout life and spleen shows no changes

liver/biliary system

liver/biliary system phenotype ( J:283977 )

N • mice show no signs of hepatosplenomegaly throughout life and liver shows no changes

reproductive system

reproductive system phenotype ( J:283977 )

N • mice are fertile and testis are normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Gaucher's disease	DOID:1926		J:283977