Analysis Tools
mortality/aging
|
• premature death
• die by 18 weeks
|
growth/size/body
|
• poor weight gain
|
nervous system
| N |
• low frequency glutamatergic synaptic transmission is normal in mutants
|
|
• hippocampal slices exposed to aCSF containing 6.5 mM potassium exhibited spontaneous interictal epileptiform bursting at a higher frequency than control slices
(J:116872)
• occasional seizures at 4 weeks of age
(J:167241)
|
|
• at 1 and 3 months, higher numbers of apoptotic cells are detected in neocortex, CA1 and CA3 pyramidal cell layers and dentate gyrus (granular and subgranular layers) compared to control brains
|
|
• gross, generalized megencephaly
|
|
• increased brain weight starting at 3 weeks of age
• become progressively more obvious with time
|
|
• progressive neuronal disorganization in hippocampus with a dispersion of the pyramidal cell layer
• greater CA1 pyramidal cell layer width in hippocampus
|
astrocytosis
(
J:167241
)
|
• increased astrocyte number in neocortex beyond 3 weeks of age
• increased astrocyte number in hippocampus beyond 1 weeks of age
|
|
• glutamate transport by astrocytes is impaired, resulting in elevated extracellular fluid glutamate (ECF) concentrations in the hippocampus at 4 weeks of age
|
|
• barium-sensitive inwardly rectifying potassium currents in cultured astrocytes show reduced amplitudes at all hyper- and depolarizing voltages used for stimulation compared with wild-type neurons; similarly currents in glia in tissue slices are reduced in response to voltage steps
• barium-sensitive conductances are lower in Tsc1-null neurons relative to wild-type
• astrocytes have significantly lower peak barium-sensitive current in response to neuronal activation than controls
|
|
• LTP induced by tetanic stimulation is significantly decreased compared to controls
• this effect is partially reversed by partial blockade of NMDA receptors with D-APV
|
behavior/neurological
| N |
• despite coordiation defects, mice are not impaired in wide variety of other tests of motor/sensorimotor function
|
|
• in conditioning chamber tests with tone/shock (T/S) pairings, mutants show impaired short term context conditioning compared to controls on day 1 of training
|
|
• when placed in chamber 24 hours after T/S training, mice show virtually no freezing indicating impaired contextual fear conditioning compared to controls
• control mice show habituation, displaying decreased freezing time, whereas mutants show potentiation of freezing
|
|
• 24 hours after contextual fear testing, mutants show less freezing behavior in response to auditory tone compared to controls
|
|
• mutants at P32 show impaired spatial learning in Morris water maze tests
|
|
• mice exhibit significantly increased times to climb down pole in pole test
|
|
• reduced swimming speed in Morris water maze trials
|
|
• hippocampal slices exposed to aCSF containing 6.5 mM potassium exhibited spontaneous interictal epileptiform bursting at a higher frequency than control slices
(J:116872)
• occasional seizures at 4 weeks of age
(J:167241)
|
cellular
|
• at 1 and 3 months, higher numbers of apoptotic cells are detected in neocortex, CA1 and CA3 pyramidal cell layers and dentate gyrus (granular and subgranular layers) compared to control brains
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| tuberous sclerosis | DOID:13515 |
OMIM:PS191100 |
J:134889 , J:167241 | |
