Phenotypes Associated with This Genotype

Genotype
MGI:5750141

• Allelic Composition: Tg(MAPT*V337M)1Gds/0
• Genetic Background: B6J.Cg-Tg(MAPT*V337M)1Gds

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

behavior/neurological

decreased anxiety-related response ( J:218742 )

• by 15-18 months of age, mutants spend more time the open arms of the elevated plus maze than controls indicating decreased anxiety

• mice treated with cycloserine, a NMDAR co-agonist, spend less time in the open arms compared to untreated mice

increased grooming behavior ( J:218742 )

• older mice exhibit repetitive grooming that increases as mice age

• repetitive grooming becomes so severe enough to cause facial lesions by about 15-18 months of age, with full penetrance by 28 months

• however, mice exhibit normal social behavior, motor coordination, and spatial learning and memory

• injection with cycloserine significantly decreases grooming behavior

abnormal nest building behavior ( J:218742 )

• mice develop nest building deficits by 3-5 months of age

• mice treated with cycloserine show improved nest building behavior

nervous system

abnormal postsynaptic density morphology ( J:218742 )

• smaller postsynaptic densities at excitatory synapses onto spines

• however, mice show normal density and size of dendritic spines of medium spiny neurons in the ventral striatum and do not exhibit neuron loss in the ventral striatum or the insular cortex

abnormal CNS synaptic transmission ( J:218742 )

• mice show a decrease in excitatory transmission and impaired network activity in the ventral striatum at 14 months of age

• mutants show no difference between the frequency of sEPSC and mEPSC events unlike wild-type mice which show more frequent sEPSC than mEPSC, suggesting less action potential-dependent input onto medium spiny neurons

decreased excitatory postsynaptic current amplitude ( J:218742 )

• mEPSC and sEPSC amplitudes are decreased, indicating decreased postsynaptic AMPAR function

abnormal excitatory postsynaptic potential ( J:218742 )

• NMDAR-dependent fEPSPs are decreased in the ventral striatum

decreased miniature excitatory postsynaptic current amplitude ( J:218742 )

• mEPSC and sEPSC amplitudes are decreased, indicating decreased postsynaptic AMPAR function

• however, mEPSC frequency is unchanged

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
frontotemporal dementia		DOID:9255	OMIM:600274	J:218742