From: Genetically modified large animal models for investigating neurodegenerative diseases
Disease | Genetic anomaly | Species | Modifications Approach | Pathology and phenotypes | References |
---|---|---|---|---|---|
Huntington’s Parkinson’s Alzheimer’s | HTT | Minipig | Lentiviral mediated Transgenesis of mHTT (N548) | - No aggregate formation and reduced intensity of DARPP32 immunoreactivity at age of 16 month - No developmental or gross motor deficits up to 40 months of age | [39] |
HTT | Minipig | CRISPR gene editing/SCNT: Knock-in HD-150Q | - Age-dependent neurological symptoms including body weight loss, early death, and movement difficulties - Selective neurodegeneration in the striatum | [20] | |
HTT | Rhesus macaque | Lentiviral mediated transgenesis of mHTT (exon1 and N512) | - Postnatal death, key clinical HD features including dystonia, chorea, and seizure - Severe neurodegeneration | [36] | |
HTT | Sheep | Embryo DNA microinjection/transgenesis | - Decreased expression of the neuronal marker DARPP-32 in medium-sized spiny neurons in the striatum at 7 months - Grow normally | [41] | |
SNCA | Primate | Transgenic: overexpression | - Age-dependent non-motor symptoms (cognitive defects, anxiety phenotype and poor fine finger coordination) | [88] | |
PINK1/Parkin/DJ-1 | Pig | KO | - No obvious neuronal loss - Normal behavior | [53] | |
PINK1/Parkin | Pig | KO | - No obvious neuronal loss - Normal behavior | [35] | |
PINK1 | Rhesus monkeys | KO | - Severe neuronal loss - Reduced motor activity | [24] | |
PINK1/DJ-1 | Rhesus monkeys | KO (adult) | - Classic PD symptoms, - Severe nigral dopaminergic neuron loss - α-synuclein pathology | [55] | |
PINK1 | Rhesus monkeys and Cynomolgus monkeys | KO (adult) | - Severe neuronal loss - Motor deficits | [31] | |
APP | Pig | Transgenic | - No pathological changes over 5Â years | ||
PSEN1 | Pig | Transgenic | - No AD-like pathological changes over 3Â years | [83] | |
APP | Cynomolgus monkeys | Transgenic | - Model established and ongoing observation | [89] | |
ALS | hSOD1 | Pig | Transgenic (SCNT) | - No ALS-like phenotype was reported - Normal development of founder pigs | [90] |
hSOD1 | Pig | Transgenic (SCNT), CMV promoter | - Movement deficits, limb muscle atrophy - Loss of motor neurons from age 8Â months - Formation of neuronal intranuclear inclusions | [73] | |
TDP-43 | Pig | Transgenic | - Severe phenotypes and early death | [67] | |
TDP-43 | Rhesus monkeys | Overexpression in adult brain | - Cytoplasmic accumulation of mutant TDP-43 - Paralyzed limb | [68] |