Phenotypes Associated with This Genotype

Genotype
MGI:3720209

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

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

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 )

• 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

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

• 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