Phenotypes Associated with This Genotype

Genotype
MGI:3832406

• Allelic Composition: Tg(SOD1*G85R)148Dwc/?
• Genetic Background: Not Specified

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

nervous system

abnormal astrocyte morphology ( J:77600 )

• at 6 months of age round Lewy body-like inclusions are visible in astrocytes

• number of inclusions increases with age

• inclusions have a dense core and a clear peripheral halo

• core consists of heterogeneous mass of short filamentous material covered with small granules

• periphery has a less dense and, in some cases, linear array of filaments

astrocytosis ( J:77600 )

abnormal neuron morphology ( J:77600 )

• abnormalities are evident in ventral motor neurons, small neurons of the central canal and interneurons of the dorsal horns, however, no abnormalities are observed in cortical or subcortical structures

abnormal motor neuron morphology ( J:77600 )

• prior to onset of disease a small number of motor neurons exhibit a few diffuse aggregates that are immunoreactive for SOD1 and ubiquitin

• aggregates progress to rounded Lewy body-like or irregular inclusions in cell bodies

• end-stage transgenics exhibit large inclusions in a few neurons in cell bodies and axonal processes

decreased motor neuron number ( J:77600 )

• loss of motor neurons in ventral horn of spinal cord

axon degeneration ( J:77600 )

• at 6.5 months a small number of large ventral motor neuron axons exhibit degeneration, although the loss is not significant

• at 8 months (disease onset) 25% of large motor axons are absent , of the remaining axons, 10% are undergoing degeneration and within another two weeks 66% are absent small caliber axons are not affected

• at 8 months 2.5% of large sensory axons are absent

• among large axons, 7.5% of dorsal root axons are absent at end stage

behavior/neurological

decreased grip strength ( J:77600 )

• weakened grip strength, the first indication of phenotype, is observed by 8 months and spreads rapidly to other limbs

paralysis ( J:77600 )

• complete paralysis occurs two weeks after onset of weakened grip strength

hindlimb paralysis ( J:77600 )

• hindlimb paralysis is first observed at 8-10 months

• paralysis occurs 2-3 days after appearance of hindlimb weakness

muscle

muscular atrophy ( J:77600 )

progressive muscle weakness ( J:77600 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:77600