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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(tetO-TARDBP*)4Vle
transgene insertion 4, Virginia M Y Lee
MGI:5000261
Summary 2 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cx1
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-TARDBP*)4Vle/0
involves: C3H/HeJ * C57BL/6J MGI:5448853
cx2
Tg(NEFH-tTA)8Vle/0
Tg(tetO-TARDBP*)4Vle/0
involves: C3H/HeJ * C57BL/6J MGI:5695547


Genotype
MGI:5448853
cx1
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-TARDBP*)4Vle/0
Genetic
Background
involves: C3H/HeJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (7 available)
Tg(tetO-TARDBP*)4Vle mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• about 50% loss of dentate gyrus neurons at 1 month after Dox removal
• massive gliosis in cortical and hippocampal regions following Dox removal
• gliosis in the corticospinal tract, including the striatum, cerebral peduncles, medullary pyramids, and cervical spinal cord, following Dox removal
• selective loss of corticospinal tract axons in cervical spinal cord associated with gliosis following Dox removal
• however, lower motor neuron loss is not observed
• mutants rarely show accumulation of hyperphosphorylated, ubiquitinated cytoplasmic aggregates of TARDBP in neurons following Dox removal (around 1% of neurons showing aggregates)
• mutants switched to a doxycycline (dox)-free diet at 28 days of age show progressive neurodegeneration; neuron loss is particularly evident in the deep neocortical layers and in the dentate gyrus but is rarely seen in the hippocampal CA1 subfield and the olfactory bulb
• selective loss of corticospinal tract axons in cervical spinal cord following Dox removal

behavior/neurological
• abnormal limb clasping as early as 1 week after dox removal that continues throughout life until sacrifice




Genotype
MGI:5695547
cx2
Allelic
Composition
Tg(NEFH-tTA)8Vle/0
Tg(tetO-TARDBP*)4Vle/0
Genetic
Background
involves: C3H/HeJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(NEFH-tTA)8Vle mutation (3 available)
Tg(tetO-TARDBP*)4Vle mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• significantly smaller brains are observed 8-10 weeks following Dox removal
• decreased cortical thickness beginning at 4 weeks following Dox removal
• brain atrophy is observed following Dox removal
• astrogliosis is observed 4 weeks after Dox removal
• denervation of neuromuscular junctions (NMJ) beginning 4 weeks after Dox removal
• by 6 weeks only 39.6% of NMJs are intact in tibialis anterior
• loss of endogenous nuclear mouse TARDBP+ 2-4 weeks following Dox removal
• accumulation of cytoplasmic ubiquitin with TARDBP+ inclusions occurs in brains and spinal cord
• 28% loss of lumbar motor neurons by 6 weeks following Dox removal; 50% loss by 8 weeks
• denervation of neuromuscular junctions (NMJ) beginning 4 weeks after Dox removal
• by 6 weeks only 39.6% of NMJs are intact in tibialis anterior
• accumulation of insoluble, phosphorylated cytoplasmic TARDBP+ inclusions in brain and spinal cord is detected as early as 1 week following Dox removal and reaches high levels by 4 weeks
• accumulation of insoluble TARDBP occurs prior to phosphorylation of protein
• inclusions are detected in motor cortex, striatum, visual and entorhinal, and somatosensory cortex, cerebellum and hippocampus
• inclusions are detected in fewer than 2% of spinal cord neurons
• by disease end stage 28% of neurons contain TARDBP+ puncta

behavior/neurological
• hindlimb clasping following Dox removal
• forelimb and/or hindlimb tremor following Dox removal
• progressive decline in balance as measured by accelerating rotarod occurs beginning 2 weeks after Dox removal
• progressive decline in coordinated movement as measured by accelerating rotarod occurs beginning 2 weeks after Dox removal
• progressive loss of grip strength as measured by wire hang test occurs beginning 2 weeks after Dox removal

mortality/aging
• median survival is 10.3 weeks off Dox
• mice die 10-18 weeks after removal of Dox; lifespan is extended if Dox is re-introduced

muscle
• decrease in mass of isolated tibialis anterior and gastrocnemius muscles following Dox removal

growth/size/body
• progressive weight loss beginning 2 weeks after Dox removal





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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
11/22/2016
MGI 6.06
The Jackson Laboratory