Analysis Tools
mortality/aging
|
• mice do not survive past 5 months of age
• after developing the first signs of unstable gait, mice reach the terminal stage of disease within a maximum of 2 weeks
|
behavior/neurological
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• at around 2.5-4.5 months of age, mice abruptly develop severe motor dysfunction
|
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• lose righting reflex and the ability to move freely within several days of onset
|
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• impaired gait caused by asymmetrical pareses and eventual complete paralysis of limbs
|
nervous system
microgliosis
(
J:203550
)
|
• rapidly developing muscle paralysis and muscle atrophy
|
astrocytosis
(
J:203550
)
|
• rapidly developing muscle paralysis and muscle atrophy
|
|
• loss of spinal motor neurons
• at the symptomatic stage, mice lose approximately half of their spinal motor neurons and the remaining neurons are shrunken and/or chromatolytic
• selective loss of lower motor neuron populations in the brainstem, including in the motor trigeminal, hypoglossal, and facial nuclei but not in the nucleus abducens
|
|
• FUS-positive inclusions are seen primarily in the lower motor neuron cell bodies, axons and, in a subset of cells, in the nucleus
• inclusions are also seen in other neurons throughout the nervous system, including upper motor neurons in the motor cortex
• large eosinophilic inclusions are occasionally seen in the spinal cord
• both cytoplasmic and nuclear inclusions in neurons are resistant to proteinase K treatment, however they are not stained by amyloid-detecting dyes Congo Red or thioflavin S
• ubiquitin-positive inclusions of various sizes and morphology are often observed in motor neurons
• however, only a fraction of FUS-positive inclusions are ubiquitinated
|
|
• FUS-positive inclusions are seen primarily in the lower motor neuron cell bodies, axons and, in a subset of cells, in the nucleus
• both cytoplasmic and nuclear inclusions in neurons are resistant to proteinase K treatment, however they are not stained by amyloid-detecting dyes Congo Red or thioflavin S
|
|
• loss of peripheral nerve fibers
• significant neuronal loss and damage of myelinated fibers in peripheral nerves is only seen at the late, generalized stage of the disease
|
homeostasis/metabolism
dehydration
(
J:203550
)
|
• mice become dehydrated
|
immune system
microgliosis
(
J:203550
)
|
• rapidly developing muscle paralysis and muscle atrophy
|
muscle
|
• rapidly developing muscle paralysis and muscle atrophy
|
hematopoietic system
microgliosis
(
J:203550
)
|
• rapidly developing muscle paralysis and muscle atrophy
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| amyotrophic lateral sclerosis type 6 | DOID:0060198 |
OMIM:608030 |
J:203550 | |
