Analysis Tools
mortality/aging
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• median survival of 35 days, with no survivors beyond 65 days
(J:121858)
• mice treated with rapamycin or RAD001 (mTOR inhibitor) show 90-100% survival to 80 days of age compared to median survival of 33 days for untreated mutants
(J:136366)
• discontinuation of drug treatment at P30 results in clinical symptom improvement for 1-2 weeks followed by clinical deterioration and death at 79 days for rapamycin-treated and 77 days for RAD001-treated mutants
(J:136366)
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growth/size/body
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• after P5 until death, mutants fail to gain weight at same rate as controls; average maximum weight is 10 grams
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nervous system
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• mice develop clinical seizures, spontaneous and some provoked in most part by physical simulation; both types of seizures are mild or severe
• severe seizures are characterized by brief behavioral arrest, followed by several seconds of clonic activity, followed by tonic extensor posturing of trunk and limbs for 15-45 seconds
• after P21, suspension by the tail results in gentle spinning leading severe seizure activity, followed by bradycardia and death
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• only mild seizures occur spontaneously, characterized by brief myoclonic jerking of head and torso
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• enlarged cells are seen outside cerebral cortex, in other parts of brain including thalamus, hypothalamus and brainstem
• no increased cell loss or degeneration is observed in regions containing anomalous enlarged cells
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• brain weight to body weight ratio is significantly greater (2.4-fold) in mutants compared to wild-type; with rapamycin/RAD001 treatment, difference from control is significantly reduced but still observed
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• enlarged cells are observed in hilus
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• enlarged cells are seen throughout pyramidal cell layer, particularly in CA3 region
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• enlarged ectopic cells are seen outside the CA1-CA3 fields in stratum oriens and stratum radiatum
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• laminar organization is less distinct than in the 6 cortical layers of controls
(J:121858)
• unusually large cells are observed in all six layers in mutants, particularly in layer V; layer of enlarged cells is seen at gray-white matter border throughout cerebral cortex at P21
(J:121858)
• mutants display subset of enlarged pS6-positive cells at base of cortex and in cortical layer V; drug treatment results in marked reduction in size of enlarged cells
(J:136366)
• mild cortical disorganization is observed in mutants with or without rapamycin treatment
(J:136366)
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• contains some enlarged cells
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• Nissl bodies and filamentous aggregates are often detected in enlarged neurons, prominently in brainstem but rarely in enlarged cortical cells
(J:121858)
• some neurons are aberrantly localized outside primary pyramidal cell layers; ectopic neurons are isolated, not organized into clusters or columns
(J:121858)
• some neurons in somatosensory cortex show 60% increase in soma size relative to controls
(J:121858)
• many pyramidal neurons demonstrate dysplastic features including increased size and thicker dendritic arbors compared to control neurons
(J:121858)
• population of neurons in lateral somatosensory cortex are considerably enlarged compared with those in controls; size is significantly reduced after drug treatment (from 1.8-fold to 1.2-fold), but effect reverses when treatment is stopped
(J:136366)
• in somatosensory cortex, layer V neurons often have major dendrites extending tangentially and diagonally to the pia, in contrast to control neurons which mainly have long apical dendrite oriented directly toward pial surface; rapamycin treatment initiated at P7 does not significantly decrease abnormally oriented dendrite percentage
(J:136366)
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• in mutant brains, neurons appear to be still actively growing after P14-21, whereas wild-type neurons have stopped growing
• this may result in the hypomyelination, due to secondary myelination failure
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• in hippocampal neuron cultures, neuronal dendritic spine density is reduced >20% compared to controls
• with rapamycin treatment, spine density is marginally increased; spine length however is increased 9% compared to treated and untreated controls or untreated mutants
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• hypomyelination is observed in brains of mutants
(J:121858)
• oligodendrocyte number and distribution appears similar to wild-type
(J:121858)
• myelination particularly in cortex is impaired due to decreased myelin production by oligodendrocytes; rapamycin treatment works to restore myelination throughout brain with greatest improvement in cortex and hippocampus
(J:136366)
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• mice aged P21-48 display 3 types of electrographic abnormalities: short spike bursts observed in all mice examined, occasionally spontaneous period of desynchronization with electrodecrement and at low incidence, frequent high-amplitude sharp waves
• interictal (seizure) 1-2 second bursts of high-amplitude 7-8 hertz spikes are observed with high frequency compared with controls; these are without obvious clinical correlate
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behavior/neurological
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• clasping behavior and tremor are significantly ameliorated by rapamycin/RAD001 treatment relative to untreated animals at 30, 60, and 100 days postnatal
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• apparent by P10
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• display posterior limb-clasping behavior when lifted by tail
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• at death, usually in third to fifth postnatal week, mice are found with extensor posture of fore- and hindlimbs
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• develops by by third or fourth postnatal week
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straub tail
(
J:121858
)
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• tail dorsiflexion is exhibited
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• mice show progressive decline in activity with limited mobility by third or fourth postnatal week
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• apparent by P10
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• mice develop clinical seizures, spontaneous and some provoked in most part by physical simulation; both types of seizures are mild or severe
• severe seizures are characterized by brief behavioral arrest, followed by several seconds of clonic activity, followed by tonic extensor posturing of trunk and limbs for 15-45 seconds
• after P21, suspension by the tail results in gentle spinning leading severe seizure activity, followed by bradycardia and death
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• only mild seizures occur spontaneously, characterized by brief myoclonic jerking of head and torso
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skeleton
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• kyphosis is significantly improved in rapamycin/RAD001-treated mice compared with untreated mutants
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cellular
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• in mutant brains, neurons appear to be still actively growing after P14-21, whereas wild-type neurons have stopped growing
• this may result in the hypomyelination, due to secondary myelination failure
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| tuberous sclerosis | DOID:13515 |
OMIM:PS191100 |
J:136366 | |
