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Table 2 SOD1 animal models

From: From animal models to human disease: a genetic approach for personalized medicine in ALS

Species Mutation Age at onset (weeks) Survival (weeks) Phenotype References
Paralysis Cognitive symptoms Neuropathological findings and particularities Gliosis
Mice hSOD1WT 58–70 normal N nd Mitochondria vacuolization and swelling,, spinocerebellar axonal degeneration, 20-30 % MN loss Y [69]
  hSOD1WT 36 52 Y nd SOD1 inclusions, vacuolization, MN loss, glial cell aggregates Y [71]
  A4V >85 normal N N nd N [70]
  A4V/SOD1WT 35 48 Y nd SOD1 inclusions, MN degeneration Y [70]
  G37R 15–17 25–29 Y Learning deficit MBV, LMN first affected, raised somatosensory thresholds Y [76, 243]
  H46R 20 24 Y nd LBHI, ubiquitin, SOD1 inclusions Y [244]
  H46R/H48Q 17–26 nd Y nd HI, ubiquitin nd [245]
  H46R/H48Q/ 35–52 nd Y nd Fibrillary SOD1-ubiquitin inclusions Y [246]
  H63G/H120G        
  D83Ga 15 70–84 N nd Sensory deficit, tremors, 20 % LMN and UMN loss Y [78]
  L84V 21–26 26–30 Y nd nd nd [247]
  G85R 35–43 37–45 Y nd Rapid progression, SOD1-ubiquitin inclusions in neurons and astrocytes Y [248]
  G85R/SOD1WT 16–21 23–30 Y nd SOD1 aggregates Y [249]
  G86Rb 13–17 17 Y nd Rapid progression (5 days) nd [250]
  D90A 52 61 Y nd Distended bladder, SOD1 inclusions, MN loss Y [75]
  G93A 13–17 17–26 Y Y MN loss, SOD1 aggregates, NMJ loss before onset Y [61, 77]
  G93A/SOD1WT 20–23 25–30 Y nd Vacuoles, MN loss Y [69]
  Thy1.2-G93Ac 54- >104 62- >104 N nd SOD1 aggregates Y [79]
  L126Z 28–44 47 Y nd Eosinophilic inclusion, MN loss, ubiquitin inclusions Y [70, 251]
  G127X 35 36 Y nd Rapid disease course, SOD1-ubiquitin inclusions Y [252]
Rats H46R 20 24 Y nd MN loss, LBHI, SOD1-ubiquitin aggregates Y [253]
  G93A 16 17 Y nd MN loss, vacuoles, SOD1-ubiquitin inclusions Y [253, 254]
Dogs T18S 7 years 21 monthsd Y nd SOD1 aggregates No neuronal cell body loss, UMN and LMN signs, sensory impairment Y [86]
  E40K >5 years 6 months–3 yearsd Y nd   Y [85]
Zebrafish A4Ve 30 h nd N nd Motor axonopathy and abnormal branching nd [90]
  G37Re 30 h nd N nd   nd [90]
  G93Ae 30 h nd N nd   nd [90]
  G93A 20–60 nd N nd Increase time resting but no swim speed change, NMJ loss, 50 % MN loss nd [91]
  G93Rf 12 months 18–27 months partial nd NMJ defects, MN loss, swimming incapacity, vacuolated mitochondria nd [92]
Fruit flies hSOD1WT 3 normal N nd Loss of climbing, no MN loss, decrease synaptic transmission in giant fiber motor pathway HSP70 stress response [93]
  A4V 4 normal N nd    [93]
  G85R 2 normal N nd    [93]
  D83S 4 normal N nd Mitochondrial pathology, decreased physical activity nd [255]
Nematodes hSOD1WT 10 days 10–20 D Y nd Reduction in thrash number nd [95]
  G85R 10 days 10–20 D Y nd Forward movement defect, SOD1 inclusions nd [95]
  G93A 2 days nd Y nd SOD1 inclusions in MN, axons guidance defects nd [256, 257]
  C6S/C57S/ normal normal N nd No phenotype nd [95]
  C111S/C146S        
Pigs G93A 12 normal N nd MN loss at 8 months, Intra-nuclear SOD1-ubiquitin inclusions, running deficit, fibrillation potentials and positive sharp waves at EMG Y [99]
  1. Y yes, N no, nd not described, MBV membrane-bounded vacuoles, HI hyaline inclusion, MN motor neuron, LMN lower motor neuron, UMN upper motor neuron, LBHI lewy-body-like hyaline inclusion, EMG electromyography, NMJ neuromuscular junctions
  2. aHomozygous mouse sod1 D83G/D83G
  3. bMouse Sod1 mutation
  4. cHomozygous SOD1G93A Thy1.2 promoter
  5. dDisease progression
  6. emRNA SOD1 injection
  7. fZebrafish transgene