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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)