Mouse Genome Informatics
tg
    Tg(SOD1*G85R)148Dwc/?
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
nervous system
• 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
• 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
• 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
• loss of motor neurons in ventral horn of spinal cord
• 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
• weakened grip strength, the first indication of phenotype, is observed by 8 months and spreads rapidly to other limbs
• complete paralysis occurs two weeks after onset of weakened grip strength
• hindlimb paralysis is first observed at 8-10 months
• paralysis occurs 2-3 days after appearance of hindlimb weakness

muscle

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:77600