Analysis Tools
behavior/neurological
 N |
• mice perform similarly to wild-type mice in the object placement test of spatial memory with a 20 minute retention interval - age not specified
• unprovoked clinical seizures are not seen
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• males exhibit deficits in visuospatial memory in the hippocampus-dependent object placement test at 20-22 weeks of age, failing to display a preference for a relocated object
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• gross ataxia and motor incoordination are not seen at 20-22 weeks of age but are readily seen at 32-34 weeks of age
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(J:229166)
• mice exhibit a higher number of slips and longer latency to cross the beam in the balance beam test, indicating motor coordination defects
(J:241124)
• however, gross ataxia is not seen
(J:241124)
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• increase in the number of rears
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• 32-34 week old males exhibit increased locomotor activity in the open field and increased exploration
(J:229166)
• mice show a longer total track length and an increase in the number of rears in the open field, indicating a modest motor hyperactivity
(J:241124)
• however, no indication of anxiety-like behavior is seen
(J:241124)
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hematopoietic system
microgliosis
(
J:262453
)
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• 22 month old mice show a microglia response, particularly in major axonal tracts such as the corpus callosum
• increases in microglia are seen in other brain regions including the cortex, striatum, hippocampus, and cerebellum
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homeostasis/metabolism
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• males show GM2 accumulation in neurons of hippocampal CA3/CA4 regions and amygdala at 4 weeks of age
(J:229166)
• GM2 ganglioside accumulation, particularly in the basolateral nuclei of the amygdala, occurs specifically in late endosomes and lysosomes
(J:241124)
• by 12 weeks of age, GM2 accumulation is also seen in neurons of CA3 and CA4 regions and the inner dentate gyrus of the hippocampus, as well as hypothalamus, fasciola cinereum, and piriform cortex
(J:241124)
• however, accumulation of GM1, GM3 or GD3 gangliosides in the brain is not seen
(J:241124)
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• no active beta-hexosaminidase enzyme activity, the lysosomal enzyme responsible for GM2 degradation, is seen in neurons storing GM2 ganglioside
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immune system
microgliosis
(
J:262453
)
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• 22 month old mice show a microglia response, particularly in major axonal tracts such as the corpus callosum
• increases in microglia are seen in other brain regions including the cortex, striatum, hippocampus, and cerebellum
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nervous system
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• small increase in hyperphosphorylated tau are seen in soluble brain fractions
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• brain size is smaller at 2 years of age
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• striatal area is decreased at 22 months but not 2 months of age
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• a subpopulation of neurons in the amygdala lack specific lysosomal storage structures
(J:229166)
• GM2 ganglioside accumulation in late endosomes and lysosomes in the basolateral nuclei of the amygdala
(J:241124)
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• by 2 months of age, the cerebrum is smaller
• cerebral brain volume shows an increase from P1 to 1 month, relative plateau at 1-2 months, slow growth but an increase at 2-6 months indicating delays in growth and a decrease at 6-23 months of age compared to wild-type mice which show an increase in volume at P0 to 1 month and 1-2 months, a plateau at 2-6 months, and decrease at 6-23 months, indicating undergrowth
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• hippocampal area is decreased at 22 months but not 2 months of age
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• cortical thickness is decreased at 22 months but not 2 months
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• cerebellar growth is similar to wild-type mice from P0 to 1 month, but mutants show decreased rate of increase from 1-2 months with a relative plateau from 2-6 months, and a severe decrease in cerebellar volume at a greater rate than the control from 6 to 23 months, indicating undergrowth from 0-6 months and significant neurodegeneration at 6-23 months in the cerebellum
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• neuron/dendritophagic clustering of CD68+ macrophages/microglia in the PC and molecular layers of cerebellar lobules I-II, III and VIII indicating Purkinje cell loss in these areas already at 4 weeks of age
(J:229166)
• cerebella shows extensive Purkinje cell loss in anterior and posterior zones at 32 weeks of age
(J:229166)
• extensive and progressive loss of Purkinje cells in the cerebellum
(J:241124)
• loss of Purkinje cells occurs in a regular pattern of parasagittal stripes in the cerebellar vermis and hemispheres
(J:241124)
• Purkinje cell loss occurs first within Zebrin II-negative stripes, while Zebrin II-postive stripes are more resistant, with Purkinje cells in lobules VI/VII and IX/X most resistant to degeneration
(J:241124)
• however, no cell loss is seen in the cerebrum
(J:241124)
• mice show progressive Purkinje cell loss in the primary fissure of the vermis largely starting after 2 months of age and worsening from 5 to 11-13 months
(J:262453)
• mice show decreased Purkinje cell density in the anterior lobe but not in the flocculonodular lobe at 5 and 11-13 months of age
(J:262453)
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• presence of Purkinje cell axonal spheroids
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• atrophy and gliosis of the cerebellar molecular layer
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• by 2 months of age, the cerebellum is smaller and remains smaller at 6 months and into old age
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microgliosis
(
J:262453
)
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• 22 month old mice show a microglia response, particularly in major axonal tracts such as the corpus callosum
• increases in microglia are seen in other brain regions including the cortex, striatum, hippocampus, and cerebellum
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astrocytosis
(
J:262453
)
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• 22 month old mice show an astrocytic response, particularly in major axonal tracts such as the corpus callosum
• increase in astrocytic response is also seen in the cerebellum and spinal cord
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• increase in the number of lysosomes in neurons storing GM2 ganglioside
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Christianson syndrome | DOID:0060825 |
OMIM:300243 |
J:229166 , J:241124 , J:262453 | |
