Analysis Tools
mortality/aging
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• about 60% of mice survive to adulthood
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• in some cases, seizures result in sudden death
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• the 10% of mice with small body size die within 3 weeks
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• mice are born in slightly less than normal Mendelian ratio
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behavior/neurological
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• mice start to exhibit hindlimb-clasping phenotype at 2-3 months of age
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• mice surviving to adulthood develop motor defects
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• adult mice fall much earlier from the accelerated rotarod
• mice have a higher number of footslips in the balance beam test
• however, adult mice exhibit normal gait in the footprint test
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• mice have a worse performance on the grip test
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• the 10% of mice with small body size exhibit abnormal posture at rest
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• the 10% of mice with small body size exhibit severe movement problems
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• seizures can be triggered by manipulations or exposure to a novel environment
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• remaining 90% of mice start to exhibit spontaneous tonic-clonic seizures at the 3rd to 4th postnatal week
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growth/size/body
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• about 10% of mice have smaller body size
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nervous system
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• seizures can be triggered by manipulations or exposure to a novel environment
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• remaining 90% of mice start to exhibit spontaneous tonic-clonic seizures at the 3rd to 4th postnatal week
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• cortical neurons show an approximate 2.5-fold slower time constant of endocytic recovery following a 10-Hz stimulus for 5 sec and the recovery is ever slower after a stronger stimulation and the signal recovers given sufficient time suggesting a kinetic delay rather than a complete block of endocytosis in presynaptic nerve terminals
• however, no defect in exocytosis is seen
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• sparse, large, abnormal clusters of both dopamine transporter and tyrosine hydroxylase, representing abnormal axons, are seen in the dorsal part of the striatum, but not the ventral striatum, at 1 month after birth, and large onion-like membrane structures in proximity of the cell bodies of striatal neurons are seen in the dorsal striatum indicating selective dystrophic changes in dopaminergic axons
• however, gliosis is not seen in brain at 8 months of age indicating that neurodegenerative changes are not seen
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• neurons exhibit massive clustering of endocytic proteins at nerve terminals
• all brain regions examined (dorsal/ventral striata, cerebellar cortex, deep cerebellar nuclei, and brainstem) show an accumulation of clathrin-coated intermediates at presynaptic terminals
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• newborn cortical neuronal cultures show synaptic clustering of several endocytic proteins and nervous tissue shows clustered synaptic immunoreactivity for endocytic proteins; the clustering phenotype is more prominent at inhibitory than at excitatory synapses
• endocytic protein clustering is partially reversed by overnight treatment with tetrodotoxin (TTX) to silence neuronal activity
• synapses show a prominent accumulation of a dense matrix such that at some synapses, this accumulation correlates with a clumping of synaptic vesicles in tight aggregates
• dystrophic axonal terminal changes are selectively seen in dopaminergic axons in the dorsal striatum
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• all brain regions examined (dorsal/ventral striata, cerebellar cortex, deep cerebellar nuclei, and brainstem) exhibit impaired synaptic vesicle recycling with an accumulation of clathrin coated vesicles in presynaptic terminals
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cellular
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• cortical neurons show an approximate 2.5-fold slower time constant of endocytic recovery following a 10-Hz stimulus for 5 sec and the recovery is ever slower after a stronger stimulation and the signal recovers given sufficient time suggesting a kinetic delay rather than a complete block of endocytosis in presynaptic nerve terminals
• however, no defect in exocytosis is seen
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Parkinson's disease 20 | DOID:0060898 |
OMIM:615530 |
J:256037 | |
