mortality/aging
• mice reach end-stage earlier
|
growth/size/body
• mice show a size difference beginning at 20 weeks of age and onwards
|
• mice fail to gain weight at the same rate as controls starting at 15 and 21 weeks of age for males and females, respectively
|
weight loss
(
J:298091
)
• weight plateaus until 60 weeks of age, at which point some mice start to show significant weight loss and reach endpoint
|
behavior/neurological
• males show reduced freezing time in the contextual fear conditioning tests
• however, females show no differences in this test
|
• males show reduced freezing time in the cued fear conditioning test
• however, females show no differences in this test
|
• mice exhibit a delayed righting reflex at 40 weeks of age; the righting time increases with age and is seen in almost all mice by 60 weeks of age
|
• about 73% of mice begin to show a limb clasping phenotype at 20 weeks of age
|
• mice exhibit ataxia, severe gait disturbances and occasional hind limb dragging near end-stage
|
• starting at 10 weeks of age, mice exhibit reduced latency to fall off the rotarod and progressively worsen with age
• mice are slower and have greater difficulty crossing the dowl and progressively worsen over time
|
• mice exhibit a reduction in muscle strength at 30 and 55 weeks of age using the inverted grid test
|
• mice exhibit reduced length of time standing on their hind limbs starting at 10 weeks of age and decreases with age
|
nervous system
• mice show increased activated microglia in the cerebellum and lower lumbar spinal cord at 30 weeks of age
|
• extensive loss of Purkinje cells is seen in 60-week old mice
|
• reduction in cerebellum size in 60-week old mice but not in 6-week old mice
|
astrocytosis
(
J:298091
)
• mice show increased astrogliosis in the cerebellum at 30 weeks of age
|
• mice exhibit an increase in the percentage of partially denervated endplates, indicating affected neuromuscular junctions
• mice exhibit smaller endplate sizes in tibialis anterior muscles
|
• mice show an increase in the number of neurofilament accumulations near the presynaptic terminals, suggesting axonal degeneration
|
• mice at end-stage exhibit spheroids in the granule cell layer
|
muscle
• average tibialis anterior and gastrocnemius muscle fiber sizes are reduced
• however, no prominent mopathic changes are seen
|
hematopoietic system
• mice show increased activated microglia in the cerebellum and lower lumbar spinal cord at 30 weeks of age
|
immune system
• mice show increased activated microglia in the cerebellum and lower lumbar spinal cord at 30 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
amyotrophic lateral sclerosis type 21 | DOID:0060212 |
OMIM:606070 |
J:298091 |