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Phenotypes Associated with This Genotype
Genotype
MGI:6095155
Allelic
Composition
Tg(tetO-TARDBP*A315T)13Lmit/0
Tg(Thy1-tTA)6Lmit/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• in the Morris water maze, 1 month old mice show a delay in memory acquisition and 3 month old mice completely fail to learn, with mice only rarely finding the hidden platform
• during probe trials of the Morris water maze, mice spend less time in the target quadrant than controls
• 3 month old mice treated with doxycycline to turn off transgene expression for 1 week exhibit a similar impairment in memory acquisition in the Morris water maze as untreated mice
• in the elevated plus maze, 1 month old mice spend 3-fold and 3 month old mice spend 5-fold more time in the open area indicating reduced anxiety or disinhibition
• 3 month old mice remain close to the edges of the area at all times of exploration in the open field
• in the elevated plus maze, 1 month old mice spend 3-fold and 3 month old mice spend 5-fold more time in the open area indicating reduced anxiety or disinhibition
• 3 month old mice treated with doxycycline to turn off transgene expression for 1 week spend a similar amount of time in the open arms of the elevated plus maze as controls
• 3 month, but not 1 month, old mice show a delay in turning at the top and reaching the bottom of a vertical pole, indicating impaired motor coordination
• 3 month, but not 1 month, old mice exhibit reduced latency to fall off the rotating rod during accelerated rotarod testing
• 3 month old mice treated with doxycycline to turn off transgene expression for 1 week are able to stay on the accelerating rotarod
• 4.5 month old mice exhibit reduced grip strength
• when exposed to a novel environment in the open field, 3 month old mice show increased distance travelled reflecting higher speed than controls
• 3 month old mice treated with doxycycline to turn off transgene expression for 1 week no longer exhibit hyperactivity in the open field

nervous system
• loss of insoluble heterogeneous nuclear ribonucleoprotein K in the brain
• gradual loss of total CA1 neurons
• hippocampal structure is already smaller at 2 weeks of age and the size of the hippocampus does not decrease significantly more until 4.5 months of age
• progressive thinning of the motor cortex
• numbers of transgene-expressing neurons in layer V progressively decrease and those in layers II/III of the cortex increase
• number of POU3F2-positive neurons is reduced progressively in layer V
• cortical width progressively reduces over time
• 6 month old mice show global forebrain atrophy, with a 21.2% reduced total brain volume
• 3 month old mice treated with doxycycline to turn off transgene expression for 1 week exhibit a comparable degree of brain atrophy as untreated mice
• large numbers of tufted enlarged GFAP+ astrocytes are seen in all neuronal layers of the motor cortex at 1 month of age, with astrocyte activation persisting over time
• 3 month old mice treated with doxycycline to turn off transgene expression for 1 week show reversal of the astrogliosis in the cortex
• however, microglial activation is not observed
• some alpha-motor neurons show dense cytoplasmic TARDBP staining at 4.5 months of age resembling inclusions
• progressive hippocampal and cortical degeneration
• degeneration of the hippocampus by 4 weeks of age

muscle
• skeletal muscle shows progressive degeneration, with increased numbers of small caliber fibers after 1 month of age
• 3 month old mice treated with doxycycline to turn off transgene expression for 1 week still exhibit muscle atrophy

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
amyotrophic lateral sclerosis type 10 DOID:0060201 OMIM:612069
J:242322 , J:245760


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
10/12/2021
MGI 6.17
The Jackson Laboratory