behavior/neurological
• mice show onset of motor abnormalities at 6 months of age
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• mice show increased hindlimb clasping starting at 6 months of age
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• mice show a progressive increase in dysfunction on the ledge test starting at 6 months of age
• mice show impaired motor coordination on the rotarod beginning at 6 months of age and progressively worsens with age
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nervous system
• mice show mislocalization of TDP-43 in lumbar spinal cord; mislocalization is prominent in motor neurons and is also present in glia
• approximately 10% of ventral horn motor neurons show TDP-43 mislocalization
• however, TDP-43 mislocalization in the cortex is not seen
• ventral horn motor neurons show nuclear membrane defects
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• degeneration of ventral horn motor neurons
• mice show a decrease in the number of spinal cord motor large caliber axons in the L5 root
• however, no significant difference in the numbers of choline acetyltransferase-positive neurons is seen in lumbar spinal cord, although a modest, non-significant, reduction is seen
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• mice show similar numbers of innervated skeletal muscle contacts, although they show a modest increase in the number of innervated neuromuscular junctions
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• primary cortical neurons show impaired nucleocytoplasmic transport
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• primary cortical neurons show a nearly 2-fold increase in cell death upon propidium iodide exclusion assay
• cultured cerebellar granule neurons show increased susceptibility to cell death upon potassium chloride withdrawal
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homeostasis/metabolism
• primary cortical neurons show a nearly 2-fold increase in cell death upon propidium iodide exclusion assay
• cultured cerebellar granule neurons show increased susceptibility to cell death upon potassium chloride withdrawal
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cellular
• primary cortical neurons show a nearly 2-fold increase in cell death upon propidium iodide exclusion assay
• cultured cerebellar granule neurons show increased susceptibility to cell death upon potassium chloride withdrawal
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
amyotrophic lateral sclerosis type 4 | DOID:0060196 |
OMIM:602433 |
J:320844 |