Analysis Tools
adipose tissue
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• decrease in abdominal white fat deposits
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behavior/neurological
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• mice show prominent and progressive hindlimb clasping from 8 weeks of age
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• mice show impairments in rotarod performance as early as 4 weeks of age, falling from the rotarod much earlier than wild-type mice
• mice show compromised ability to walk on a cage ledge starting from 4 weeks and worsening over time
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• 7 of 8 males and all females are unable to run at the lowest treadmill speed at 24 weeks of age
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spasticity
(
J:334532
)
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• mice exhibit difficulty with ambulation, exhibiting hindlimb weakness and stiff, slow movements characteristic of spasticity
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cardiovascular system
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• female mice exhibit lung arterial hyperplasia and hypertrophy
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cellular
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• mice show transverse endoplasmic reticulum (ER) expansion in myelinated corticospinal axons; transverse ER manifests as a pattern repeating about every 0.3-1 um across nearly the full diameter of the axon, resembling the rungs of a ladder in longitudinal sections
• ER in axons shows prominent transverse, sheet-like structures and these periodic structures are connected to one another via a few longitudinal ER tubules and have apertures that allow mitochondria, microtubules and neurofilaments to pass through
• the vast majority of corticospinal axons and only a few ventral root axons have expanded transverse ER
• transverse ER expansions are present in lumbar (L5) and cervical (C4) spinal cord at 1 month of age but are larger and more numerous at 6 months and transverse ER is more prominent in lumbar regions
• transverse ER is also present in spinothalamic axons in spinal cord as well as peripherally in sciatic nerve
• transverse axonal ER expansions sometimes are associated with, or give rise to, less-organized ER tubule aggregations at 6 months of age
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• levels of ER stress protein GRP78/immunoglobulin-binding protein (BiP) are increased, indicating ER stress in the spinal cord, however at P180, levels are dramatically decreased in the spinal cord
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growth/size/body
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• mice show lower body weights starting at 8 weeks in males and 16 weeks in females
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muscle
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• muscle wasting
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• skeletal muscle atrophy of the front and hind limbs
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nervous system
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• corticospinal tracts exhibit prominent changes in shape and size of axons and degeneration by 6 months of age
• transverse endoplasmic reticulum (ER) expansion is seen in myelinated corticospinal axons
• mitochondria appear more fragmented in corticospinal axons and mitochondrial volume is slightly increased in corticospinal axons, with more dramatic decreases in mitochondrial length
• however, ER-mitochondrial contact surfaces areas are similar to wild-type
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• mice have multiple swollen myelin sheaths and digestion chambers in the peripheral nervous system
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• 4.5-month-old mice have rare to occasional spheroids in the brainstem as well as in the spinal cord
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reproductive system
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• about 30-50% of breeding pairs are poor breeders
• mice have short breeding periods (from ages 2-5 months)
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respiratory system
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hereditary spastic paraplegia | DOID:2476 |
OMIM:PS303350 |
J:334532 | |
