Mouse Genome Informatics
tg
    Tg(Myl1-SOD1*G93A)#Amu/0
FVB/NJ-Tg(Myl1-SOD1*G93A)#Amu
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
muscle
• Z lines of adjacent myofibrils tend to lose register with one another
• fibers in EDL muscles show partial loss or misalignment of sarcomeres
• sarcoplasmic reticulum in muscle fibers is often abnormally fragemented and fragmented vesicles are seen just below the sarcolemma
• 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
• 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
• 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

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
• mitochondria in muscle fibers have an edematous internal matrix with abnormal and/or missing internal cristae
• mitochondria in muscle fibers are frequently abnormally shaped
• mitochondria in muscle fibers are frequently larger in size
• malondialdehyde is elevated in the sarcolemma of muscle fibers and in the spinal cord, indicating lipid oxidative damage in these areas

homeostasis/metabolism
• superoxide dismutase and catalase activity are increased in muscles compared to wild-type mice
• glutathione reductase activity in muscles is reduced

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

nervous system
• however, motor neuron degeneration is not observed
• microglia activation is seen in the spinal cord, but astrocyte activity is similar to wild-type

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

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:143747