Analysis Tools
behavior/neurological
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• 18 month old mice clasp their rear limbs during tail suspension
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• mice show decreased spontaneous horizontal movement in the open field
• however, 18 month old mice show normal rotarod performance and rearing behavior
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homeostasis/metabolism
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• mice show selective defects in autophagy function
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nervous system
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• brains exhibit an increase in gliosis throughout many brain regions, including, but not limited to, cortex, striatum, hippocampus, cerebellum, thalamus, and midbrain, at 18 months of age
• gliosis in the cortex is seen as early as 1 month of age which increases with age
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astrocytosis
(
J:221680
)
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• mice exhibit large ubiquitin-positive protein aggregates by 12 months of age, most prominent in the cortex and hippocampus; inclusions localize within neurons
• neurons accumulate lipid droplets which are larger and more numerous than in controls and are associated with lipofuscin
• however, no alpha-synuclein abnormalities are seen and no ubiquitin- or alpha-synuclein-positive aggregates are seen in dopaminergic cells and mice exhibit normal numbers of dopaminergic neurons
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pigmentation
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• mice exhibit increased lipofuscinosis in multiple brain regions at 3 months of age
• lipofuscin deposits consist of large, electron dense material, frequently containing membranous structures, in close association with large lipid droplets
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cellular
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• age-dependent accumulation of lysosomal proteins and lipids lysosomal accumulation in multiple brain regions
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• mice show selective defects in autophagy function
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• endolysosomal pathway dysfunction characterized by decreased cathepsin D processing and decreased clearance of autophagic substrates, however lysosomal function appears normal
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• accumulation of lysosomal proteins by 6 months of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Kufor-Rakeb syndrome | DOID:0060556 |
OMIM:606693 |
J:221680 | |
