Phenotypes Associated with This Genotype

Genotype
MGI:3833385

• Allelic Composition: Tg(Thy1-MAPT*K369I)K3Gotz/0
• Genetic Background: B6.Cg-Tg(Thy1-MAPT*K369I)K3Gotz

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

behavior/neurological

enhanced behavioral response to xenobiotic ( J:143439 )

• mice exhibit a strong cataleptic response to lower doses of the dopamine antagonist haloperidol compared to wild-type mice

abnormal object recognition memory ( J:143439 )

• at 4 months, mice exhibit a lack of preference for a novel object compared to wild-type mice indicating impaired working memory

abnormal motor capabilities/coordination/movement ( J:143439 )

• mice exhibit postural instability as indicated by repeated slipping while crossing a narrow beam unlike wild-type mice

limb grasping ( J:143439 )

• at 4 weeks of age

tremors ( J:143439 )

• beginning at 4 weeks of age and becoming severe by 8 weeks of age

impaired coordination ( J:143439 )

• mice exhibit reduced motor coordination on a challenging beam compared to wild-type mice

• mice exhibit postural instability as indicated by repeated slipping while crossing a narrow beam unlike wild-type mice

• motor coordination of old mice is not improved with L-dopa treatment

• however, motor coordination of young mice is improved with L-dopa treatment

abnormal gait ( J:143439 )

• at 4 weeks of age

short stride length ( J:143439 )

• by 38% at 4 weeks of age

bradykinesia ( J:143439 )

• at 4 weeks of age, mice exhibit repeated and prolonged resting phases in an open field compared to in wild-type mice

• at 2 months, mice exhibit reduced locomotor activity and rearing in an open field compared to wild-type mice

nervous system

nervous system phenotype ( J:143439 )

N • despite muscular atrophy, no overt neurodegeneration is detected

abnormal neuron morphology ( J:143439 )

• at 5 months, mice develop Bielschowsky silver+ intraneuronal inclusions unlike in wild-type mice

loss of dopaminergic neurons ( J:143439 )

• age-dependent beginning at 12 months of age in the substantia nigra

abnormal axon morphology ( J:143439 )

• at 2 months, a few axonal swellings are detected unlike in wild-type mice

• spheroids are detected at 5 months and become larger and more numerous by 10 months unlike in wild-type mice

abnormal axonal transport ( J:143439 )

• axonal transport is selectively impaired in the nigrostriatal system

• at 3 months, anterograde transport of TH in the substantia nigra pars compacta neurons is impaired

• anterograde axonal transport of APP- and TH-containing vesicles and mitochondria is impaired

• anterograde transport in the sciatic nerve is impaired

• however, retrograde transport and transport of non-APP- and TH-containing vesicles and mitochondria are normal

muscle

muscular atrophy ( J:143439 )

• muscular atrophy begins at 4 weeks of age

• mice exhibit amyotrophy unlike wild-type mice

• however, no motor neuron degeneration is evident

growth/size/body

decreased body weight ( J:143439 )

• female and male mice are lighter than wild-type mice by 30% and 27%, respectively

homeostasis/metabolism

decreased dopamine level ( J:143439 )

• at 6 weeks, basal dopamine levels in the brain are decreased 15% compared to in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
frontotemporal dementia		DOID:9255	OMIM:600274	J:143439