Phenotypes Associated with This Genotype

Genotype
MGI:5499112

• Allelic Composition: Tg(Myl1-SOD1*G93A)#Amu/0
• Genetic Background: FVB/NJ-Tg(Myl1-SOD1*G93A)#Amu

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

muscle

abnormal sarcomere morphology ( J:143747 )

• fibers in EDL muscles show partial loss or misalignment of sarcomeres

abnormal Z line morphology ( J:143747 )

• Z lines of adjacent myofibrils tend to lose register with one another

abnormal sarcoplasmic reticulum morphology ( J:143747 )

• sarcoplasmic reticulum in muscle fibers is often abnormally fragemented and fragmented vesicles are seen just below the sarcolemma

abnormal skeletal muscle fiber morphology ( J:143747 )

• 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 ( J:143747 )

• 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

abnormal muscle physiology ( J:143747 )

• 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

abnormal mitochondrial morphology ( J:143747 )

• 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

abnormal mitochondrial crista morphology ( J:143747 )

• mitochondria in muscle fibers have an edematous internal matrix with abnormal and/or missing internal cristae

abnormal mitochondrial shape ( J:143747 )

• mitochondria in muscle fibers are frequently abnormally shaped

increased mitochondrial size ( J:143747 )

• mitochondria in muscle fibers are frequently larger in size

oxidative stress ( J:143747 )

• malondialdehyde is elevated in the sarcolemma of muscle fibers and in the spinal cord, indicating lipid oxidative damage in these areas

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:143747 )

• superoxide dismutase and catalase activity are increased in muscles compared to wild-type mice

• glutathione reductase activity in muscles is reduced

increased catalase activity ( J:143747 )

• in muscles

immune system

increased microglial cell activation ( J:143747 )

• 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

increased microglial cell activation ( J:143747 )

• microglia activation is seen in the spinal cord, but astrocyte activity is similar to wild-type

• however, motor neuron degeneration is not observed

hematopoietic system

increased microglial cell activation ( J:143747 )

• 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		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:143747