muscle
• fibers in EDL muscles show partial loss or misalignment of sarcomeres
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• Z lines of adjacent myofibrils tend to lose register with one another
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• sarcoplasmic reticulum in muscle fibers is often abnormally fragemented and fragmented vesicles are seen just below the sarcolemma
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• fibers in EDL muscles show altered internal organization, partial loss or misalignment of sarcomeres, changes of mitochondrial morphology and of their sarcomeric disposition, and disorganization of the sarcotubular system
• transverse-tubule organization is altered in muscle, with T-tubules curving into an L-like structure that progresses to a vesicle-like structure encompassing amorphous cellular material instead of running perpendicularly to the long axis of the fiber
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• skeletal muscle atrophy is first detectable at 4 weeks of age and increases into adulthood
• mice treated with Trolox, a cell-permeable water-soluble derivative of vitamin E, show a reduced toxic effect of ROS, rescuing the muscle phenotype
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• decreased tetanic and specific force generation of 37% for extensor digitorum longus and 39% for soleus muscle
• analysis of isotonic fatigue shows that stimulation of extensor digitorum longus (EDL) and soleus in the first seconds of fatigue produces work of about 38% less than wild-type muscles, and EDL and soleus stop shortening about 7 seconds and 15 seconds, respectively, before wild-type controls
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cellular
• mitochondria in fibers are often clustered in abnormal longitudinal rows between the myofibrils and/or large clusters located just under the sarcolemma
• mitochondria in muscle fibers are frequently abnormally shaped, larger in size, and have a translucent appearance, edematous internal matrix with abnormal and/or missing internal cristae, vacuolization, and myelin-like figures
• disrupted mitochondria in muscle fibers appear to be enveloped in membranous sacks
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• mitochondria in muscle fibers have an edematous internal matrix with abnormal and/or missing internal cristae
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• mitochondria in muscle fibers are frequently abnormally shaped
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• mitochondria in muscle fibers are frequently larger in size
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• malondialdehyde is elevated in the sarcolemma of muscle fibers and in the spinal cord, indicating lipid oxidative damage in these areas
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homeostasis/metabolism
• superoxide dismutase and catalase activity are increased in muscles compared to wild-type mice
• glutathione reductase activity in muscles is reduced
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• in muscles
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immune system
• microglia activation is seen in the spinal cord, but astrocyte activity is similar to wild-type
• however, motor neuron degeneration is not observed
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nervous system
• microglia activation is seen in the spinal cord, but astrocyte activity is similar to wild-type
• however, motor neuron degeneration is not observed
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hematopoietic system
• microglia activation is seen in the spinal cord, but astrocyte activity is similar to wild-type
• however, motor neuron degeneration is not observed
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
amyotrophic lateral sclerosis type 1 | DOID:0060193 |
OMIM:105400 |
J:143747 |