Mouse Genome Informatics
cx1
    Tg(GSK3B*S9A)1Vln/0
Tg(Thy1-MAPT)1Vln/Tg(Thy1-MAPT)1Vln

involves: FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
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 (J:100971)
• double mutants are unable to remain on the rotating rod

nervous system
• 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
N
• quadriceps is normal and devoid of any muscle wasting (J:100971)

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:100971


Mouse Genome Informatics
tg2
    Tg(Thy1-MAPT)1Vln/Tg(Thy1-MAPT)1Vln
involves: FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body

nervous system
N
• no significant loss of neurons in ventral horn of spinal cord is observed (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
• mice show increased levels of astrogliosis in affected regions of spinal cord and cortex compared to wild-type or other transgenic lines
• scattered throughout brain and spinal cord gray matter are thickened and irregularly shaped dystrophic argyrophilic neurites
• 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)
• 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
• mice show postural instability
• when lifted by tail, homozygotes flex the hind limbs, in contrast to wild-type which extend legs
• 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)
• 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
• muscle mass is decreased, contributing to 30% decrease in body weight
• significant muscle atrophy is observed, with little or no atrophy seen in heterozygous mice or homozygous Tg(Thy1-MAPT)5Vln (J:100972)
• quadriceps and gastrocnemius muscles contain groupings of atrophic fibers and fascicular atrophy
• shown by inability to maintain grasp of inverted wire mesh

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:100971 , J:100972


Mouse Genome Informatics
tg3
    Tg(Thy1-MAPT)1Vln/0
FVB/N-Tg(Thy1-MAPT)1Vln
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• severe clasping of limbs when lifted by the tail
• severe motor defect by 6-8 weeks
• no mouse was able to stay on the bean even at 3 moths of age

nervous system
• 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
• Wallerian degeneration following axonopathy

muscle
• muscle wasting following axonopathy


Mouse Genome Informatics
tg4
    Tg(Thy1-MAPT)1Vln/0
involves: FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• dilated axons are observed in brain and spinal cord

behavior/neurological
• compared to wild-type mice, mutants are 13 times more likely to fall off of a rotating rod in a rotarod test
• heterozygous mice display higher swimming speeds than wild-type mice