Analysis Tools
mortality/aging
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• no mice survive beyond 3 weeks of age
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Allele Symbol Allele Name Allele ID |
Tardbptm3.1Ckjs targeted mutation 3.1, C K James Shen MGI:6404633 |
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| Summary |
3 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• no mice survive beyond 3 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• males show a shorter life span, with an average of 19.5 +/- 2 months
• survival of females is longer than males, with average age being 25.5 +/- 6 months
• male-to-female ratio of the surviving pups is 1 to 2.6
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• males exhibit motor dysfunction at 6 months of age or older
• however, young and old males do not show impaired performance on the T-maze task
• disease onset in females is highly variable and about 30% of females are indistinguishable from wild-type females
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• males start to show hind limb-clasping around 8 months of age
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• males show a shorter latency to fall than wild-type mice starting after 5 months of age
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• males develop hindlimb paralysis with age
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• mice exhibit spastic and trembled gait at 18 months and beyond
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• males lose weight after 18 months of age
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• 12 and 24 month old males exhibit skeletal muscle atrophy, with a decrease in wet weight of soleus muscle and reduction of calf muscle volume
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• astrogliosis is seen in the spinal cord in aged, but not 6 month, mice
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• the level of ubiquitinated proteins is increased in the ChAT+ motor neurons of spinal cord of 6 month or older males, most of which are in the cytosol
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• males show an age-dependent loss of spinal cord motor neurons, with nearly 30%, 62%, and 77% loss at 6 months, 12 months, and 24 months, respectively
• 30% loss of motor neurons in the lumbar region of the spinal cord at 6 months of age while the motor cortex, especially the primary motor cortex, only shows NeuN+ neuron loss at 24 months of age, indicating that lower motor neurons are affected first and then pathology spreads to the upper motor neurons
• however, males do not show loss of neurons in the dentate gyrus, CA1 or CA3 regions of hippocampus
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• 6 month old males show denervation of the neuromuscular junction of soleus muscle which progresses with ageing
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• TDP-43+ aggregates appear in the cytosol of spinal cord motor neurons of 12 and 24 month old males and colocalize with ubiquitinated proteins
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| amyotrophic lateral sclerosis type 10 | DOID:0060201 |
OMIM:612069 |
J:285792 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• embryonic stem cell-derived spinal motor neurons show increased cytosolic calcium ion concentrations
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• embryonic stem cells differentiated to motor neurons in culture show a reduction in survival on day 14 in culture
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• embryonic stem cells differentiated to motor neurons in culture show a reduction in average axon length on day 14 in culture
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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 04/16/2024 MGI 6.23 |
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