Analysis Tools
mortality/aging
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• animals rarely survive beyond 16 days of age
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growth/size/body
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• animals are similar size to controls until postnatal day 8, after which they are smaller
(J:13950)
• mutant mice are significantly smaller than controls at 1 week of age
(J:132285)
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• at P9, mutant mice weigh approximately 50% of controls
(J:34237)
• mutant mice do not gain any additional body weight after P9, while control mice increase by 56% between P9 and P15
(J:34237)
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behavior/neurological
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• mice exhibit rigidity when touched
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• at one week of age, mice exhibit an inability to turn over when placed on the back
(J:34237)
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• unccordinated movements are observed at 1 week of age
(J:34237)
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• animals are usually totally paralysed at postnatal day 16
(J:13950)
• at 2-3 weeks of age, muscles of mutant mice become increasingly paralyzed, especially in the pelvic girdle and hindlimb regions
(J:34237)
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muscle
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• rarely, some muscle fibers show mitochondrial defects
• no signs of inflammation, degeneration or necrosis
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• the number of muscle fibers is similar to controls, but all mutant muscle fibers are smaller than controls; the cross sectional area is reduced and muscle fibers are more tightly packed, leaving little intercellular space
(J:106411)
• mutant skeletal muscle fibers appear smaller
(J:132285)
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• rarely, some muscle fibers show centrally positioned nuclei
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• observed at 1 week of age
(J:34237)
• individual muscles are atriophied compared to age-matched controls
(J:106411)
• the total protein content of the mutant gastrocnemius and sternoclastoid muscles was less than half of controls at P6
(J:106411)
• total muscle protein content remains the same from P6 to P14 while content in controls increases further
(J:106411)
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• observed at 1 week of age
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• starting around 8 days of age
(J:13950)
• mice exhibit a rapid loss of motor function in all limbs by P12-14
(J:132285)
• mice lose the ability to support their own weight
(J:132285)
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nervous system
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• multiple large vacuoles with clear content are present in neuronal cell bodies at P14; mitochondrial defects are seen including displacement of the inner membrane, cristae disruption and increased volume of the intermembrane space
• vacuoles are already present in 76% of the dorsal root ganglion neurons by P1
• no evidence of neuronal loss of spinal cord anterior horn motorneurons, sensory dorsal root ganglion neurons, and Purkinje cells is seen
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• spinal motor neurons in mutant mice appear smaller than controls and show a decrease in both soma and nuclear area at P8-9 and at P14
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• at P8-9, lumbar motorneurons from mutant mice appear similar to controls
• by P14, there is a 30-35% decrease in the number of spinal motorneurons in the lateral motor column compared to controls
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• measurments of axon diameters within the sciatic nerve showed that mutant mice lacked large caliber axons
(J:106411)
• large caliber axons are absent from the spinal cord and sciatic nerve
(J:132285)
• some axonal damage is seen in sciatic nerve including Schwann cell infoldings into the axoplasm and disintegration of adaxonal myein lamellae
(J:132285)
• sciatic nerve also contain damaged mitochondria with swollen cristae
(J:132285)
• no evidence for axonal degeneration is seen; total number of axons is similar to controls
(J:132285)
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• in the sciatic nerve at P9-13, the nodes of Ranvier appear elongated in mutant mice, with occasional asymmetry in the myelin thickness on the two sides of the widened node
• in the sciatic nerve, a reduced frequency of lamellar fusion within the myelin of the paranodal region is seen, leaving long cytoplasmic extensions within the myelin
• in some internodal regions of the sciatic nerve, a few promyelinated axons are seen
• intramuscular axons are completely unmyelinated within the muscle
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• synapses form normally but but show progressive atrophy and eventual loss of motor nerve terminals
(J:13950)
• by postnatal day 16, every endplate in some muscles is totally denervated
(J:13950)
• at P9-P13, junctional AChR clusters are 30% longer than in controls
(J:106411)
• at P9, AChR receptor numbers are similar in mutant and control muscles
(J:106411)
• at P7, the preterminal axons are thinner and more numerous than controls
(J:106411)
• at P12, mutant terminals have thin axon terminal branches and the arborization is not complex; many terminals are multiply innervated
(J:106411)
• at P14, some endplates are contacted by large numbers of small nerve terminals and many show regions of vacant postsynaptic membrane that are covered with collagen
(J:106411)
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• by P14, there is a 30-35% decrease in the number of spinal motorneurons in the lateral motor column compared to controls
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• mutant spinal cord shows a reduction in myelinated fiber density with the remaining fibers exhibiting small diameters; no large caliber axons are seen
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• mutant spinal cords exhibit a reduced diameter compared to controls
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• intramuscular nerve fibers degenerate on rare occasions but nerve roots and anterior horn cells are normal
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• at P1, the number of myelinated axons in the corticospinal tract is similar to controls
• by P7, only a few myelinated axons are present in the corticospinal tract of mutant mice
• at P14, most axons in the corticospinal tract are myelinated in control mice whereas in the mutant mice, only 60% of the axons are myelinated and many small unmyelinated axons are present
• at P5, myelination is also delayed in the sciatic nerve, which shows a reduced number of myelinated axons compared to controls
• myelination of the dorsal roots is delayed by P5 and in the ventral roots by P1
• neurofilament content of mutant axons shows a reduced density in mutant mice; it appears in dense clusters with uneven distribution compared to controls
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• electrophysiology studies show abnormalities in spontaneous miniature endplate potentials and in their parameters after nerve stimulation
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cellular
| N |
• no impairment in mitochondrial protein synthesis in different tissues is seen
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• a decrease in complex activity I in brain or spinal cord-derived mitochondria from mutant mice is seen compared to controls, attributable to a reduced amount of assembles complex I
• a decrease in the amount of complex III is also seen in brain or spinal cord-derived mitochondria from mutant mice
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liver/biliary system
| N |
• no evidence of abnormal mitochondria morphology in liver sections
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