behavior/neurological
• mice develop progressive spastic gait, with normal gait at 2 months of age but with an increase in the numbers of slips and falls at 3 months of age and show gait differences at 6 months of age
• - mice exhibit difficulty crossing a beam at 6 months of age
• mice show a decrease in foot-base-angle at 3 months of age; the foot-base-angle is decreased to about 65 degrees at 3 months of age and progressively decreases with growth to about 50 degrees at 6 months of age
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• mice show a decrease in the ability to grasp sticks with the hind limbs, indicating hind limb muscle weakness
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spasticity
(
J:332139
)
• mice develop progressive spastic gait
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nervous system
• mice exhibit smaller endosomes and an increase in vesicle number in spinal cord neurons and alternations in distribution of Rab proteins suggesting abnormal endosome formation and fusion
• lumbar spinal cord neurons show an accumulation of ubiquitinated proteins and autophagosomes which co-localize
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• the number of neurons in the spinal cord is reduced in 7-month-old mice
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• 7-month-old mice exhibit hypertrophy of the anterior horn cells
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• myelinated fibers in the spinal cord are distributed unimodally, with small 7 um fibers being most abundant compared to bimodally distributed fibers with 7 um and 10 um fibers being most abundant in wild-type mice, indicating selective loss of thick myelinated fibers close to the spinal cord surface and axonal degeneration
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homeostasis/metabolism
• lumbar spinal cord neurons show an accumulation of autophagosomes which co-localize with the aggregated ubiquitinated proteins, indicating autophagy dysfunction
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cellular
• lumbar spinal cord neurons show an accumulation of autophagosomes which co-localize with the aggregated ubiquitinated proteins, indicating autophagy dysfunction
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
hereditary spastic paraplegia 80 | DOID:0112341 |
OMIM:618418 |
J:332139 |