Analysis Tools
mortality/aging
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• 35.1% of females die by 1 year of age and an additional 46.4% of females develop symptoms of motor neuron disease
• males do not show decreased survival at 1 year of age
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nervous system
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• mice that develop a slower progressive disease exhibit intermittent seizures
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microgliosis
(
J:239579
)
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• acute end-stage mice exhibit reactive gliosis in the hippocampus
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• acute end-stage mice show degeneration, pyknosis, and vacuolization of the large pyramidal neurons in layer V of the motor cortex
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• acute end-stage mice show a 28% decrease in thickness of the molecular layer
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astrocytosis
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J:239579
)
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• acute end-stage mice show astrocytosis in layers I-III and layer V of the motor cortex and the hippocampus
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• between 20-40 weeks of age, a subset of about 30-35% of females develop an acute, rapidly progressive motor neuron disease characterized by inactivity, labored breathing, sudden weight loss, hindlimb weakness, paralysis and decrease in survival
• a large percentage of remaining female mice develop a milder and slower progressive disease characterized by kyphosis, reduced activity, hyperactivity when provoked, clasping and intermittent seizures
• about 43-45% of males develop progressive motor neuron disease phenotypes by 1 year of age
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• acute end-stage mice show a loss of NeuN- and CV-positive interneurons in the lateral and posterior horns of the spinal cord
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• end-stage mice show denervation of the neuromuscular junctions in the tibialis anterior and diaphragm muscles, with a dramatic loss of axon terminals but normal pretzel-shaped morphology
• slow progressive mice exhibit subtle neuromuscular junction abnormalities including increased axonal swelling and axon terminal sprouting, indicating degeneration and regeneration
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• acute end-stage mice show a loss of axonal integrity within the lumbar 4 ventral spinal roots, with increased numbers of small axons, indicating degeneration and regeneration, and fewer large caliber alpha-axons
• slower progressing mice show milder phenotypes in spinal roots with a shift to smaller fiber sizes
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• RAN protein aggregates throughout the brain of acute end-stage mice and in 18 month old slow progressive mice
• acute end-stage mice show nuclear and cytoplasmic TARDBP (TDP-43) aggregates in degenerating neurons throughout the brain
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• acute end-stage mice show cortical and hippocampal neurodegeneration
• males and females with slowly progressing disease show milder neurodegenerative changes, with mice at 18 months of age showing focal rather than widespread degeneration in the neocortex, milder degeneration in the cerebellum and no overt degeneration in the hippocampus
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• loss of neurons in cornu ammonis and dentate gyrus regions of the hippocampus, with some mice showing degeneration of the CA1 region and others of the CA3 and dentate gyrus or the entire CA region
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• acute end-stage mice show a 65% loss of Purkinje cells
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• acute end-stage mice show a loss in motor neurons in the ventral horn of the lumber spinal cord, as well as atrophic and vacuolated motor neurons
• slow progressing mice also show lower motor neuron loss
• end-stage mice show extensive neuronal loss, pyknosis, and abundant vacuolization in layers II/III throughout the cortex and in layer V of the motor cortex, with a 75% decrease in layer II/III neurons and 57% decrease in layer V
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• acute end-stage mice show degeneration of the axons that terminate in targeted skeletal muscles at the neuromuscular junctions
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behavior/neurological
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• older symptomatic males and females spend 50% less time in the central region of the open field, indicating anxiety-like behavior
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• seen in mice that develop a milder and slower progressive motor neuron disease
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• mice develop hindlimb gait abnormalities at 16 weeks of age
• a subset of older symptomatic males and females show decreases in ambulation
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• inactivity and reduced activity are seen in mice that develop a rapidly and slower progressive motor neuron disease, respectively
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• mice that develop a milder and slower progressive motor neuron disease exhibit hyperactivity when provoked
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paraparesis
(
J:239579
)
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• mice that develop rapidly progressive motor neuron disease exhibit hindlimb weakness
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• mice that develop a slower progressive disease exhibit intermittent seizures
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hematopoietic system
microgliosis
(
J:239579
)
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• acute end-stage mice exhibit reactive gliosis in the hippocampus
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growth/size/body
weight loss
(
J:239579
)
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• mice that develop rapidly progressive motor neuron disease exhibit sudden weight loss
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immune system
microgliosis
(
J:239579
)
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• acute end-stage mice exhibit reactive gliosis in the hippocampus
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muscle
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• end-stage mice show mild muscle abnormalities, including atrophic fibers, sharp angular fibers, and pyknotic nuclear clumps in fast-twitch muscles
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• focal, but not widespread, skeletal muscle atrophy in end-stage mice
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skeleton
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• seen in mice that develop a milder and slower progressive motor neuron disease
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| frontotemporal dementia and/or amyotrophic lateral sclerosis 1 | DOID:0060213 |
OMIM:105550 |
J:239579 | |
