Phenotypes Associated with This Genotype

Genotype
MGI:5569760

• Allelic Composition: Tg(Prnp-MAPT)7Vle/0
• Genetic Background: involves: C57BL/6 * SJL

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

nervous system

neurofibrillary tangles ( J:61052 )

• inclusions in the somatodendritic compartment of cortical neurons resemble neurofibrillary tangles

tau protein deposits ( J:61052 )

• tau-positive spheroidal inclusions in spinal cord neurons are visible by 1 month of age

• size and number increases up to 6-9 months of age, but decreases in number by 12 months of age

• inclusions are the size of medium to large spinal cord neurons and some appear to arise within the proximal axons of spinal cord neurons

• spinal cord inclusions are most frequent at the grey-white matter junction

• spinal cord inclusions in line 7 are smaller and less abundant than in line 43

• tau-positive intraneuronal aggregates are seen in the brain, but they are smaller and appear later than in the spinal cord

• tau-positive inclusions appear in cortical neurons and brainstem by 6 months of age

• inclusions in cortical neurons occur in proximal axons or somadendritic domains of neurons

• inclusions are visible in pontine neurons by 1 month of age and in the cerebral cortex at 6 months of age

• tau deposits become increasingly insoluble with age

astrocytosis ( J:61052 )

• detectable after one month of age

abnormal motor neuron morphology ( J:61052 )

• in addition to inclusions, vacuolar lesions are observed in older mice

motor neuron degeneration ( J:61052 )

abnormal axon morphology ( J:61052 )

• spinal cord ventral root contains irregularly shaped axons at 6 months of age

• by 12 months of age endoneurial space in ventral root axons appears to increase

axon degeneration ( J:61052 )

• 20% decrease in number of ventral root axons by 12 months of age

• significant reduction in microtubule density by 12 months of age, although neurofilament density is unchanged

abnormal axonal transport ( J:61052 )

• fast axonal transport of proteins is retarded in 12 month old mice as compared to wild-type

behavior/neurological

limb grasping ( J:61052 )

• mice retract hindlimbs when lifted by the tail

impaired balance ( J:61052 )

• impaired ability to stand on a slanted surface

weakness ( J:61052 )

• progressive motor weakness

growth/size/body

decreased body weight ( J:61052 )

• mice weigh 30-40% less than normal littermates

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:61052
frontotemporal dementia		DOID:9255	OMIM:600274	J:61052