Phenotypes associated with this allele

• Allele Symbol: Tg(Thy1-MAPT)1Vln
• Allele Name: transgene insertion 1, Fred Van Leuven
• Allele ID: MGI:3720113
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(GSK3B*S9A)1Vln/0 Tg(Thy1-MAPT)1Vln/Tg(Thy1-MAPT)1Vln	involves: FVB	MGI:3722101
tg2	Tg(Thy1-MAPT)1Vln/Tg(Thy1-MAPT)1Vln	involves: FVB	MGI:3720209
tg3	Tg(Thy1-MAPT)1Vln/0	FVB/N-Tg(Thy1-MAPT)1Vln	MGI:3771316
tg4	Tg(Thy1-MAPT)1Vln/0	involves: FVB	MGI:3720210

Genotype
MGI:3722101

cx1

• Allelic Composition: Tg(GSK3B*S9A)1Vln/0; Tg(Thy1-MAPT)1Vln/Tg(Thy1-MAPT)1Vln
• Genetic Background: involves: FVB

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

behavior/neurological

behavior/neurological phenotype ( J:100971 )

N • mice show equal performance to wild-type in the hanging grid test and forced swim test, and show almost no impairment of the righting reflex

impaired coordination ( J:100971 )

• double mutants are unable to remain on the rotating rod

nervous system

abnormal axon morphology ( J:100971 )

• in 3-month old mice, dilated axons are observed, but numbers are reduced ~5-fold in spinal cord and ~20-fold in cerebral cortex compared to Tg(Thy1-MAPT)1Vln homozygotes

• axonal dystrophic changes are dramatically reduced in mice expressing both transgenes

muscle

muscle phenotype ( J:100971 )

N • quadriceps is normal and devoid of any muscle wasting

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:100971

Genotype
MGI:3720209

tg2

• Allelic Composition: Tg(Thy1-MAPT)1Vln/Tg(Thy1-MAPT)1Vln
• Genetic Background: involves: FVB

growth/size/body

decreased body weight ( J:100972 )

nervous system

nervous system phenotype ( J:100972 )

N • no significant loss of neurons in ventral horn of spinal cord is observed

tau protein deposits ( J:100972 )

• phosphorylated tau protein is detected in pyramidal neurons in the cortex and hippocampus, in axonal processes in the corpus callosum and mossy fibers of the hippocampal granular cells in mice at 2.5 months of age

• nerve cell bodies and axonal processed in the spinal cord also display presence of phosphorylated tau protein at 2.5 months

astrocytosis ( J:100972 )

• mice show increased levels of astrogliosis in affected regions of spinal cord and cortex compared to wild-type or other transgenic lines

abnormal neuron morphology ( J:100972 )

• scattered throughout brain and spinal cord gray matter are thickened and irregularly shaped dystrophic argyrophilic neurites

abnormal axon morphology ( J:100971 , J:100972 )

• in 3 month old mice, dilated axons are detected in the spinal cord and cerebral cortex (J:100971)

• cytoskeletons of dilated axons are disrupted, with numerous randomly oriented microtubules engirdling accumulations of pleomorphic vesicles, dense-cored vesicles, and smooth endoplasmic reticulum; ratio of microtubules to neurofilaments in dilated axons is high relative to normal axons (J:100971)

• grouping of atrophic fibers and fascicular atrophy are observed (J:100971)

• some axons in brain and spinal cord are grossly dilated, having rounded contours often as large as neighboring cell bodies; numbers of dilated axons (axonopathy) is greater in homozygotes than heterozygous or wild-type littermates, or homozygous Tg(Thy1-MAPT)5Vln mice (J:100972)

• dilated axons in brain are most often observed in neocortex, hippocampus, and thalamus, and found mainly in proximal gray matter (J:100972)

• in spinal cord dilated axons are located primarily in gray matter, with some found in white matter fiber tracts (J:100972)

• at 8 weeks and 8 months of age, axons show prominent accumulation of neurofilaments, microtubules, mitochondria, endoplasmic reticulum, and vesicles (J:100972)

axon degeneration ( J:100972 )

• degenerating axons and neurites are similar to dystrophic axons in Alzheimer disease or other neurodegenerative diseases

• some dilated axons show signs of degeneration, varying from only some degenerating mitochondria to axons with numerous dense and multivesicular bodies

• myelin sheath is often thinned and detached

• Wallerian degeneration is observed, indicated by presence of microglia containing myelin debris and myelin ovoids

• distal part of axons from lumbosacral motor neurons in sciatic nerve display Wallerian degeneration, and thinned myelin sheaths or axons with axon-Schwann cell networks are sometimes seen

behavior/neurological

abnormal postural reflex ( J:100972 )

• mice show postural instability

impaired righting response ( J:100971 )

limb grasping ( J:100972 )

• when lifted by tail, homozygotes flex the hind limbs, in contrast to wild-type which extend legs

impaired coordination ( J:100971 , J:100972 )

• compared to wild-type mice, mutants are 90 times more likely to fall off of a rotating rod in a rotarod test; mice are less able to retain grip on an inverted mesh grid and fall with greater frequency and in shorter times than wild-type or lower-expressing transgenic mice (J:100972)

abnormal locomotor activation ( J:100972 )

• in Morris water maze, swimming speed is significantly less than wild-type or Tg(Thy1-MAPT)5Vln mutants; in 1 minute, mice cover only 70% that of wild-type littermates

muscle

decreased skeletal muscle mass ( J:100972 )

• muscle mass is decreased, contributing to 30% decrease in body weight

muscular atrophy ( J:100971 , J:100972 )

• significant muscle atrophy is observed, with little or no atrophy seen in heterozygous mice or homozygous Tg(Thy1-MAPT)5Vln (J:100972)

skeletal muscle fiber atrophy ( J:100972 )

• quadriceps and gastrocnemius muscles contain groupings of atrophic fibers and fascicular atrophy

muscle weakness ( J:100972 )

• shown by inability to maintain grasp of inverted wire mesh

cellular

abnormal cell cytoskeleton morphology ( J:100971 )

• cytoskeletons of dilated axons are disrupted, with numerous randomly oriented microtubules engirdling accumulations of pleomorphic vesicles, dense-cored vesicles, and smooth endoplasmic reticulum; ratio of microtubules to neurofilaments in dilated axons is high relative to normal axons

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:100971 , J:100972

Genotype
MGI:3771316

tg3

• Allelic Composition: Tg(Thy1-MAPT)1Vln/0
• Genetic Background: FVB/N-Tg(Thy1-MAPT)1Vln

behavior/neurological

limb grasping ( J:96869 )

• severe clasping of limbs when lifted by the tail

abnormal motor coordination/balance ( J:96869 )

• severe motor defect by 6-8 weeks

• no mouse was able to stay on the bean even at 3 moths of age

nervous system

abnormal axon morphology ( J:96869 )

• progressive axonopathy with numerous axonal dilations in brain and spinal cord

• reaction with thioflavin S or X-34 was completely absent confirming the total absence of tauopathy

axon degeneration ( J:96869 )

• Wallerian degeneration following axonopathy

muscle

muscular atrophy ( J:96869 )

• muscle wasting following axonopathy

Genotype
MGI:3720210

tg4

• Allelic Composition: Tg(Thy1-MAPT)1Vln/0
• Genetic Background: involves: FVB

nervous system

abnormal axon morphology ( J:100972 )

• dilated axons are observed in brain and spinal cord

behavior/neurological

impaired coordination ( J:100972 )

• compared to wild-type mice, mutants are 13 times more likely to fall off of a rotating rod in a rotarod test

abnormal locomotor activation ( J:100972 )

• heterozygous mice display higher swimming speeds than wild-type mice