Phenotypes Associated with This Genotype

Genotype
MGI:5829782

• Allelic Composition: Tg(Prnp-MAPT*K274Q*K281Q)286Lgn/0
• Genetic Background: involves: C57BL/6 * FVB/N

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

impaired contextual conditioning behavior ( J:230252 )

• during contextual discrimination training, mutants exhibit worse discrimination between two similar contexts compared to controls

• however, mutants are able to distinguish between two very different contexts

impaired discrimination learning ( J:230252 )

• in an object-context discrimination task, mutants show no preference for exploring the incongruent object during the test phase as do controls at 6-7 months of age, suggesting that mice are unable to differentiate between previous experiences

abnormal long-term spatial reference memory ( J:230252 )

• mice exhibit impaired spatial memory in the Morris water maze, with mice showing no preference for the target quadrant in the 72 hour probe trial

nervous system

abnormal dentate gyrus morphology ( J:230252 )

• mice show lower KIBRA (WWC1) protein levels in spines of dentate granule cells

tau protein deposits ( J:230252 )

• mice show pathological tau accumulation (caspase-cleaved tau and higher MC1 immunoreactive tau) in hippocampal mossy fibers

astrocytosis ( J:230252 )

• astrogliosis in the dentate gyrus

impaired synaptic plasticity ( J:230252 )

• synaptic plasticity in hippocampus is impaired

abnormal excitatory postsynaptic potential ( J:230252 )

• field excitatory postsynaptic potential (fEPSP) slope is decreaed in the dentate gyrus molecular layer

reduced long-term potentiation ( J:230252 )

• after theta-burst stimulation of the perforant pathway to dentate granule cell synapses, potentiation significantly declines in dentate gyrus molecular layer brain slices by 60 min after LTP induction

• however, basal synaptic transmission is normal and AMPAR- and NMDA receptor-mediated synaptic strength is normal

• treatment of brain slices from 5-6 month old mice with jasplakinolide, a membrane-permeable drug that promotes actin polymerization, restores LTP to control levels

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:230252