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Table 5 C9ORF72 animal models

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

Species Number of repeats Promoter Age at onset (weeks) Survival (weeks) Phenotype References
Paralysis Cognitive symptoms Neuropathological findings and particularities Gliosis
Mice 80 TRE none normal N N ubiquitin-positive inclusion, no DPR, no TDP-43 inclusion nd [174]
  66a nd 24 nd nd Y Nuclear RNA foci, phosphoTDP-43 inclusions, cytosolic and nuclear DPR, Anxiety and social abnormalities, motor impairment Y [176]
  100–1000 BACb none normal N N RNA foci, DPR, no NCI N [178]
  500 BACb none normal N N RNA foci, DPR, no NCI N [177]
  450 BACb 52 normal N Y RNA foci, DPR, age-dependant protein accumulation, no motor deficits or MN loss, age dependant cognitive deficit, no TDP-43 mislocalization N [179]
  500 BACb 16 20–40c Y Y NMJ loss, reduced axonal size, MN loss, RNA foci, DPR, TDP-43 NCI Y [180]
Fruit flies 36–103 elav-GS nd 30 days nd nd RNA foci, DPR, toxicity was attributed to DPR nd [182]
  160 actin5C-Gal4 none normal N nd RNA foci, DPR, toxicity was attributed to DPR nd [181]
  30 Ok371-Gal4 4 nd nd nd Decreased locomotor activity nd [183]
  58 Ok371-Gal4 nd nd nd nd Decreased locomotor activity, NMJ loss, DPR nd [184]
Nematodesd n/a alfa-1 2 nd Y nd MN loss, paralysis in 60 % of worms nd [185]
Zebrafishe n/a n/a nd nd nd nd MN axons shortening, reduced swimming nd [186]
  1. Y yes, N no, nd not described, n/a not applicable, BAC bacterial artificial chromosome, DPR dipeptide repeat, NCI neuron cytoplasmic inclusion, MN motor neuron, NMJ neuromuscular junction
  2. aIntracerebroventricular injection of AAV2/9 containing 66 G4C2 repeat lacking ATG start codon at post-natal day 0
  3. bBAC include sequence of the human C9ORF72 exons with promoter
  4. c35 % of female mice died from 20–40 weeks, most of other mice develop cognitive symptoms at older age
  5. d C. elegans orthologue alfa-1(ok3062) mutation
  6. eKnockdown of zebrafish C9orf72 orthologue (C13H9orf72)