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Allele Symbol Allele Name Allele ID |
Tg(Prnp-TARDBP*A315T)95Balo transgene insertion 95, Robert Baloh MGI:4358722 |
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| Summary |
8 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Background Sensitivity: survival in F1 males is increased by 50-90 days as compared to males on the C57BL/6J background
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• all F1 mice die with visible signs of gut pathology similar to mice on the C57BL/6J background
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Background Sensitivity: survival in F1 males is increased by 50-90 days as compared to males on the C57BL/6J background
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• all F1 mice die with visible signs of gut pathology similar to mice on the C57BL/6J background
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• late onset difficulty in righting occurs suddenly and progresses rapidly especially in males
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• mild deficit in the hindlimb reflex is observed in both male and female mice
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• time-to-fall as measured by the hanging wire test is significantly decreased in transgenic males as compared to wild type littermates
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• both male and female mice exhibit a tendency to drag their tails when walking
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• late onset immobility occurs suddenly and progresses rapidly especially in males
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• progressive decrease in number of fecal pellets excreted
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• gut motility is significantly decreased beginning at day 60 in males and progresses to 282% of controls by day 90
• gut motility is significantly decreased in females but at later age than males and with less severity
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• lower GI tract develops swelling, intra-intestinal coagulated blood, and necrotic tissue, however, pathology of upper digestive tract is normal
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• weight loss becomes significant at post-natal day 85 in males and post-natal day 127 in females
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• late onset swollen and tender abdomen occurs suddenly and progresses rapidly especially in males
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• late onset dehydration occurs suddenly and progresses rapidly especially in males
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• late onset unkempt haircoat occurs suddenly and progresses rapidly especially in males
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• ovariectomy decreases female median survival by 94 days
• male castration decreases median survival by 10 days
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• Background Sensitivity: death occurs at a median of 108 days in males
• Background Sensitivity: death occurs at a median of 185 days in females
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• ganglions in the superior mesentery appear smaller than control ganglions
• ganglions exhibit an increased percentage of condensed nuclei
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• decreased AChE staining in the ganglion and intermodal strands of the myenteric plexus of the colon
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• 80% decrease in the number of neurons per ganglion in the myenteric plexus of the colon, but not the duodenum, of 90-150 day old mice
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• reactive astrocytosis observed in spinal cord lumbar sections from 80 day old males
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• the large motor neurons of some males exhibit abnormally shaped nuclei
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• small, but significant decrease in axon number and diameter in the sensory branch of the femoral nerve in 3 and 5 month old males
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• some motor neurons have ubiquitin-positive cytoplasmic inclusions
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• late onset kyphosis occurs suddenly and progresses rapidly especially in males
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Background Sensitivity: survival in F1 males is increased by more than 340 days as compared to males on the C57BL/6J background
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• all F1 mice die with visible signs of gut pathology similar to mice on the C57BL/6J background
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|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• Background Sensitivity: survival in F1 males is increased by 50-90 days as compared to males on the C57BL/6J background
|
|
• all F1 mice die with visible signs of gut pathology similar to mice on the C57BL/6J background
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• average survival is 154 days; at end-stage, mice die spontaneously or are euthanized when they lose righting reflex or can no longer obtain food and water
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• mice begin losing weight around 4.5 months of age
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• at 3-4 months mice develop abnormal gait; around 4.5 months, mice exhibit a "swimming" gait when they lose ability to support their body weight but still use their limbs for propulsion to slide on their stomachs
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• activation of astrocytes is detected in layer 5 with reactive astrocytosis seen around degenerating neurons
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• late-stage mice have cytoplasmic accumulation of ubiquinated proteins in neurons of cortical layer 5; these neurons are prominent in the motor cortex and are also present in orbital, cingulated, sensory and other cortical regions
• no ubiquinated protein aggregates are observed in the caudate/putamen, substantia nigra, thalamus or other structures at any stage
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• neuron loss in cortical layer 5
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• fewer axons are observed in the lower thoracic spinal cord with numerous degenerating axons being seen in dorsal corticospinal tract and lateral columns
• femoral motor and sensory nerves shows loss of axons with ongoing axonal degeneration in the motor branch
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• fewer axons are observed in the lower thoracic spinal cord with numerous degenerating axons being seen in dorsal corticospinal tract and lateral columns
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• in end-stage mice, about a 20% loss of spinal motor neurons is observed
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• presence of ubiquitinated protein accumulations is detected preferentially in large neurons of the dorsal horn as well as scattered interneurons
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• end-stage mice have scattered and grouped atrophic muscle fibers, characteristic of muscle denervation
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• atrophic muscle fibers are observed in end-stage mice
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• electromyography in end-stage mice shows numerous fibrillation potentials indicative of loss of muscle fiber innervation and fasciculations, which are spontaneous firing of motor units often seen with human motor neuron diseases; in presymptomatic and early-stage mice, electromyography is normal
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• around 4.5 months, mice can no longer support their body weight
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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:153197 | |
| frontotemporal dementia | DOID:9255 |
OMIM:600274 |
J:153197 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• Background Sensitivity: survival in F1 males is increased by more than 340 days as compared to males on the C57BL/6J background
|
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• all F1 mice die with visible signs of gut pathology similar to mice on the C57BL/6J background
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• Background Sensitivity: survival in F1 males is increased by more than 340 days as compared to males on the C57BL/6J background
|
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• all F1 mice die with visible signs of gut pathology similar to mice on the C57BL/6J background
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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 04/30/2024 MGI 6.23 |
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