Table 2.

UBQLN2 animal models

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]

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