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] |