Table 2.

Outline of advantages and disadvantages of using minipigs as animal models for HD

Advantages	Disadvantages
Large gyrencephalic brain with similar neuroanatomy and blood supply to humans	Two layers of frontal bone with large inter-bone gap
Similar neurodevelopmental processes and comparable white matter ratio and degree of myelination to humans, striatum is prominent and divided into separate caudate and putamen
Similar immune system to human	Susceptible to PERV (porcine endogenous retroviruses)
Long lifespans (10–20 years)
Omnivores, digestive system similar to humans, body weight 80–110 kg
Amenable to frequent blood &CSF collections
Able to reproduce at 6 months
Gestation only 4 months
6–8 piglets per litter, thus relatively easy preparation of experimental groups for preclinical studies
Relatively easy to maintain in controlled conditions in stables	Boars have to be stabled separately or castrated.
Inexpensive to maintain compared to NHP
Minipigs can learn some cognitive and motoric tests	Minipigs are tetrapods and so gait and balance are dissimilar to those of humans.
Minipigs do not have forearms and fine motor skills can be tested only by tongue test
Genetically modified models exist:
1. TgHD (N-548)
–Models long premanifest stage	–Slow phenotype progression; manifest symptoms late
–CAG/CAA repeat structure
–Useful for HTT lowering PK-PD, safety studies	–two endogenous minipig Htt alleles intact
–Model access through CHDI/IAPG
2. KI-HD-85Q (minipig Htt; 82 pure CAG repeats)
–Model access through CHDI/IAPG	–100% porcine Htt sequence
–Useful for HTT lowering PK-PD, safety studies	–Phenotype not well described
3. KI-HD-150Q (human HTT exon 1; 150 pure CAG repeats)
–Models manifest disease	–Only 40% of F1 piglets survived longer than 5 months
	–Severe disease symptoms may be too rapid for interventional testing
	–Unknown ability to access model