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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)
Rats KO
130 N Y Hippocampal and cortical neuronal loss, UBQLN2/P62 NCI (no TDP-43),
KO rats exhibit no phenotype
Mice WT
P497S P506T
90 N Y UBQLN2 AAV expression,
hippocampal and cortical NCI (with UBQLN2, TDP-43, p62, ubiquitin and OPTN), motor phenotype
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
Mice mP520T (KI) 270 N Y Hippocampal, cortical and brainstem NCI (with UBQLN2 and p62)
no motor phenotype
Rats WT
40 N Y Similar phenotype in WT and P497H
hippocampal and cortical neuronal loss,
NCI (UBQLN2, p62, ubiquitin and RPT1),
no motor phenotype
P497H P525S
Y N NMJ loss in P497H,
eye degeneration in mutant,
NCI (UBQLN2, ubiquitin and p62)
motor phenotype
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
DM KO 3 N N NCI (UBQLN2, TDP-43 and ubiquitin)
motor phenotype
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