Phenotypes Associated with This Genotype

Genotype
MGI:2446420

• Allelic Composition: Tg(SOD1*G93A)2Gur/0
• Genetic Background: involves: C57BL/6 * SJL

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

mortality/aging

premature death ( J:32665 )

• animals are moribund by 5 months of age

growth/size/body

weight loss ( J:89928 )

• weight loss starting around 13 weeks of age

behavior/neurological

abnormal grooming behavior ( J:32665 )

• impaired grooming evident at 3 to 4 months

limb grasping ( J:32665 )

• mutants extend their hind legs less than normal when lifted by the tail

tremors ( J:32665 , J:89928 )

• develop a tremor of the hindlimbs when suspended in the air (J:32665)

• fine hind limb tremors starting around 12 weeks (J:89928)

impaired coordination ( J:89928 )

• consistently worse performance than the control animals on the rotarod

• decline steadily after 15 weeks of age for the rotarod, around 12 weeks for the hanging wire

• unable to remain on the rotarod at 19 weeks of age, or 20 weeks for the hanging wire

• the hanging wire test has a higher diagnostic accuracy

abnormal limb posture ( J:32665 )

• normal limb posture when not moving, however after initiation of movement, hindlimbs and toes frequently lock in a hyperextended position

paralysis ( J:32665 )

• 4mutants become paralyzed in one or more limbs after 5 months of age

muscle

progressive muscle weakness ( J:32665 )

• hindlimb weakness evident at 3 to 4 months

nervous system

abnormal brainstem morphology ( J:78629 )

• intraneuronal vacuoles and vacuoles in the surrounding neuropil

brain vacuoles ( J:78629 )

• intraneuronal vacuoles and vacuoles in the surrounding neuropil in the brainstem

abnormal axon morphology ( J:78629 )

• swollen axons with a dense or vacuolated axoplasm at 163 days of age

• irregular myelin sheeths in contour

• irregular frayed myelin sheeths

abnormal ventral spinal root morphology ( J:78629 )

• decreased numbers of axons in anterior root at 113 days of age

• swollen axons, with a dense or vacuolated axoplasm

• irregular myelin sheeths in contour

• irregular frayed myelin sheeths

• macrophages with myelin debris

abnormal spinal cord morphology ( J:78629 )

abnormal motor neuron morphology ( J:78629 )

• exquisite localization of vacuoles to the cytoplasm of the large motor neurons of the spinal anterior horns, particularly in the lateral portions at 73 days of age

• vacuoles inside the neuronal cell bodies and in the surrounding neuropil at 163 days of age

motor neuron degeneration ( J:32665 , J:78629 )

• loss of choline acetyltransferase-containing spinal motor neurons, particularly in the ventral spinal cord (J:32665)

• decreased size of the anterior horns at 180 days of age (J:78629)

• severe loss of motor neurons (J:78629)

• surviving neurons are atropic with an irregular contour and eosinophilic hyaline inclusions (J:78629)

abnormal spinal cord ventral horn morphology ( J:78629 )

• exquisite localization of vacuoles to the cytoplasm of the large motor neurons of the spinal anterior horns, particularly in the lateral portions at 73 days of age

• vacuoles inside the neuronal cell bodies and in the surrounding neuropil at 163 days of age

• decreased size of the anterior horns at 180 days of age

• swollen axons, some with axoplasmic vesicles in their course from the anterior horn to the anterior root at 163 days of age

abnormal spinal cord dorsal column morphology ( J:78629 )

• mild swelling nerve fibers in the intermediate zone of the posterior columns and posterior roots

abnormal spinal cord lateral column morphology ( J:78629 )

• swollen axons, with a dense or vacuolated axoplasm in lateral columns at 180 days of age

• irregular frayed myelin sheeths

abnormal spinal cord ventral column morphology ( J:78629 )

• vacuolation of axoplasm at 163 days of age

• axonal swellings with a dense axoplasmic appearance

• irregular myelin sheeths in contour

• irregular frayed myelin sheeths

• swollen axons, with a dense or vacuolated axoplasm in anterior columns at 180 days of age

axon degeneration ( J:32665 )

• loss of large myelinated axons in intramuscular nerves and from ventral motor roots

axonal spheroids ( J:78629 )

• rarely greatly expanded axonal profiles pack with dense fibrillary

cellular

abnormal endoplasmic reticulum morphology ( J:78629 )

• vacuoles in the rough endoplasmic reticulum

abnormal mitochondrial morphology ( J:78629 )

• vacuoles in the mitochondrion

• large vacuoles cause linearization of the entire structure

integument

coarse hair ( J:32665 )

• coats develop a coarse appearance

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:32665 , J:78629 , J:89928