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Phenotypes Associated with This Genotype
Genotype
MGI:3802584
Allelic
Composition
Tsc1tm1Djk/Tsc1tm1Djk
Tg(GFAP-cre)8Gtm/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(GFAP-cre)8Gtm mutation (1 available)
Tsc1tm1Djk mutation (1 available); any Tsc1 mutation (48 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
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
• 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:191100
OMIM:613254
J:134889 , J:167241


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
07/10/2018
MGI 6.12
The Jackson Laboratory