Phenotypes Associated with This Genotype

Genotype
MGI:3717255

• Allelic Composition: Tg(Thy1-MAPT)22Schd/0
• Genetic Background: B6.Cg-Tg(Thy1-MAPT)22Schd

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

mortality/aging

premature death ( J:111982 )

• low level of mortality is displayed by transgenic mice, with 2 females (5-7 months of age) and 3 males (17 months of age) dying during course of study, compared to 0 controls

growth/size/body

decreased body weight ( J:111982 )

• bodyweights of males and females are reduced by ~15% compared to wild-type littermates

behavior/neurological

behavior/neurological phenotype ( J:111982 )

N • transgenic mice show no dysfunction of motor skills, motor impairment, or paralysis up to 18 months of age

abnormal spatial learning ( J:111982 )

• over a 4-day period, transgenic mice show significant delay in learning the location of the hidden platform in the Morris water maze task on days 2 and 3 compared to wild-type controls

• spatial memory is also significantly impaired in mice aged 10-14 months compared to wild-type controls

decreased anxiety-related response ( J:111982 )

• mice spend more time in the open arms of an elevated-plus maze compared to wild-type littermate controls

nervous system

nervous system phenotype ( J:111982 )

N • in 6-7 month old mice, LTP remains normal

abnormal brain morphology ( J:111982 )

• by 3 months of age, abnormal MAPT (tau) species are observed early in CA1 pyramidal layer of hippocampus and spreading to detante gyrus and CA3; also seen in striatum, olfactory bulb, occipital cortex, amygdala, ventral thalamic nuclei, and deep layers of entorhinal cortex

abnormal hippocampus morphology ( J:111982 )

• a slight reduction in number and size of tau-positive neurons in frontal cortex, CA1 and CA3 regions, and in neurites and fiber tracts of entire hippocampus is observed in mice >12 months of age

neurofibrillary tangles ( J:111982 )

• ghost tangles are detected in CA1 by 12 months; in pyramidal neurons, fibrillary inclusions are ~19.4 nm in diameter, with largest having diameter of 31.9 nm, showing regular constrictions every ~129 nm

tau protein deposits ( J:111982 )

• before abnormal tau species are detected in neuron soma, they are detected in axonal tracts and neurites; older mice show intracellular inclusions in neuronal perikarya and in proximal portions of dendrites

• mice >12 months of age show hyperphosphorylation and pathological tau phosphorylation, formation of neurofibrillary tangle-like inclusions, tau filaments and ghost tangles (Alzheimer disease-like pathology)

• at 6 months of age, neurons containing tau deposits are detected in the pyramidal cell layer of the CA1 region and in the prefrontal cortex; number increases with age, and by 12 months, such neurons are found in the dentate gyrus, CA3 region, and amygdala

gliosis ( J:111982 )

• increase in number of glial cells is detected in hippocampal hilus, cerebral cortex, corpus callosum, CA1, and CA3 region in aged mice

abnormal neuron morphology ( J:111982 )

• neurons containing pathological tau species increases with age

abnormal axon morphology ( J:111982 )

abnormal CNS synaptic transmission ( J:111982 )

• synaptic function (transmission) is decreased by 80% relative to wild-type

decreased excitatory postsynaptic current amplitude ( J:111982 )

• synaptic excitability is reduced in 14-15 month animals; mean amplitude of EPSPs at high stimulation intensity is 0.289 mV vs 1.24 mV in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:111982