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Table 2 UBQLN2 animal models

From: Key role of UBQLN2 in pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia

Species

Mutations

Age at onset (days)

Motor neuron loss

Cognitive deficits

Neuropathological particularities

Ref.

Mice

P497H

30

N

Y

Dendritic spinopathy. Hippocampal NCI

(no TDP-43 but with proteasome component, VCP and OPTN)

[21]

Rats

KO

P497H

130

N

Y

Hippocampal and cortical neuronal loss, UBQLN2/P62 NCI (no TDP-43),

KO rats exhibit no phenotype

[65]

Mice

WT

P497H

P497S P506T

90

N

Y

UBQLN2 AAV expression,

hippocampal and cortical NCI (with UBQLN2, TDP-43, p62, ubiquitin and OPTN), motor phenotype

[5]

Mice

WT

P497S P506T

90

Y

Y

Hippocampal and MN NCI (with UBQLN2, TDP-43 and Ubiquitin),

motor phenotype, muscle atrophy, NMJ loss, axonal degeneration, gliosis

some MN loss and axonal degeneration in WT

[34]

Mice

mP520T (KI)

270

N

Y

Hippocampal, cortical and brainstem NCI (with UBQLN2 and p62)

no motor phenotype

[24]

Rats

WT

P497H

40

N

Y

Similar phenotype in WT and P497H

hippocampal and cortical neuronal loss,

NCI (UBQLN2, p62, ubiquitin and RPT1),

no motor phenotype

[25]

DM

WT

P497H P525S

P4X

28

7

14

0

Y

N

NMJ loss in P497H,

eye degeneration in mutant,

NCI (UBQLN2, ubiquitin and p62)

motor phenotype

[31]

Rats

P497H

90

Y

N

Muscle atrophy, axonal degeneration, NMJ loss, MN NCI (UBQLN2, p62, p-TDP-43), motor phenotype

no phenotype when expressed in astrocytes

[7]

DM

KO

3

N

N

NCI (UBQLN2, TDP-43 and ubiquitin)

motor phenotype

[27]

Mice

UBP497H/TDP-43G348C

150

Y

Y

Hippocampal and MN NCI (UBQLN2, TDP-43, pTDP-43, ubiquitin and p62), muscle atrophy, axonal degeneration, gliosis, motor phenotype

[50]

  1. WT wild-type, Y yes, N no, n/a not applicable, HTT huntington disease protein, NCI neuronal cytoplasmic inclusions, MN motor neurons, NMJ neuromuscular junction, KI knock-in, DM Drosophila melanogaster