Analysis Tools
mortality/aging
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• homozygotes show reduced (80%) survival, with the earliest death occurring at 7 months of age
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behavior/neurological
| N |
• no handling-induced seizures are observed
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limb grasping
(
J:79615
)
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• at 10-12 months, tail hang/clasping assays revealed clasping in 42% of homozygous mutant mice, compared with 10% of wild-type or heterozygous mutant mice
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abnormal gait
(
J:79615
)
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• at 10-12 months, gait analyses indicated shortened average stride length (rear paw) and increased base width (rear paw stance)
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• at 10 -12 months of age
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liver/biliary system
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• in liver, ATP synthase subunit c-reactive deposition is observed as early as E19.5
• at 10 months, mutant hepatocytes contain abundant autofluorescent, ATP synthase subunit c-reactive membrane deposits
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vision/eye
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• retinal neurons contain membrane deposits in the RGC layer and the inner nuclear layer (INL), with small punctate granules in the outer nuclear layer (ONL)
• retinal deposits are first observed at P1.5, within the neuroblastic layer
• punctate subunit c-reactive granules are noted within the ONL and INL in the mature retina at P8 and P30
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• at 10-17 months, retinas of hypopigmented homozygotes show a 37% reduction in the number of cone cells per field relative to retinas of hypopigmented heterozygotes
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• retinal ganglion cells show electron-dense membranous perinuclear inclusions with a JNCL-like 'fingerprint' profile
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• retinas from pigmented homozygotes do not exhibit a cone cell loss at 10-17 months, suggesting that hypopigmentation may accelerate retinal degeneration
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nervous system
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• at 10 months, homozygotes display membranous deposits in the CNS
• autofluorescent, ATP synthase subunit c-reactive membrane deposits are observed in the cytoplasm of CA2 and CA3 pyramidal cells of the hippocampus, Purkinje cells of the cerebellum, as well as cortical neurons and thalamic neurons
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• accumulates are first noted at E19.5 in neurons of the dentate gyrus and in the subventricular zone at the lateral ventricle
• in these regions, ATP synthase subunit c-reactive deposits are undetectable after P8
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• ultrastructurally, CA2/3 hippocampal pyramidal neurons show abundant perinuclear, osmiophilic and electron-dense inclusions
• such subunit-c inclusions have multilamellar membranes, a JNCL-like 'fingerprint' appearance, and are first detected at P8, increasing in size and intensity by P30
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• cerebellar deposits are detected in the Purkinje cell layer at E19.5, increasing in severity by P30
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• accumulates are first noted at E19.5 in neurons of the dentate gyrus and in the subventricular zone at the lateral ventricle
• in these regions, ATP synthase subunit c-reactive deposits are undetectable after P8
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• at 10 months, all homozygotes exhibit reactive gliosis in the motor cortex, white matter tracts of the cerebellum and midbrain, including the inferior colliculus
• no apoptotic changes are observed in these regions
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• at 10-17 months, retinas of hypopigmented homozygotes show a 37% reduction in the number of cone cells per field relative to retinas of hypopigmented heterozygotes
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• retinal ganglion cells show electron-dense membranous perinuclear inclusions with a JNCL-like 'fingerprint' profile
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neuronal ceroid lipofuscinosis 3 | DOID:0110731 |
OMIM:204200 |
J:79615 | |
