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Table 2 Large animal models of neurodegenerative diseases

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 5 years [81, 82]
PSEN1 Pig Transgenic - No AD-like pathological changes over 3 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 8 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]