Table 1. Animal Models of HD.

Model	Construct/Promoter	PolyQ Length	Age of Onset	Pathology	Behavioral Phenotype	Year
Mouse R6/1	Human Htt promoter; ~1.9kb fragment of 5´ human HD gene	115	5 m	Intranuclear and neuropil aggregates throughout the brain; global brain atrophy; minimal cell death	Tremors and gait abnormalities; rotarod deficit; clasping behavior; learning deficit	1996 [23]
R6/2		144	2 m
Drosophila	GAL4-UAS system- using eye-specific P element expression vector pGMR; human HD exon 1	75 or 120	2 or 10 days	Late-onset progressive neurodegeneration dependent on repeat length; nuclear accumulation but no inclusions	Expression restricted to eyes	1998 [19]
Zebrafish	Expanded N-terminal fragment of Htt protein fused with GFP	102	24 h post fertilization	Increase in apoptotic cells, inclusions in non-apoptotic cells	Increase in embryonic lethality or in embryos with abnormal morphology	1998 [134]
Mouse N171-82Q	N-terminal 171 amino acids of human Htt; mouse prion promoter	82	5 m	Inclusions in striatum, cortex, hippocampus and amygdala; striatal degeneration	Tremors and gait abnormalities; rotarod deficit; loss of coordination; hypokinesis	1999 [135]
Conditional mouse	TetO regulatable; Chimeric mouse/human exon 1. Replace the endogenous	94	4.5 m	Nuclear/ cytoplasmic aggregates in striatum, cortex, and hippocampus; striatal degeneration; gliosis	Clasping behavior, tremor, decreased grooming	2000 [60]
Mouse Hdh Q150	polyQ with expanded polyQ; mouse Hdh promoter	150	4 m	Nuclear inclusions in striatum; striatal gliosis	Clasping behavior; gait abnormalities; rotarod deficit; hypoactivity	2001 [136]
Mouse YAC 128	YAC expressing full-length human Htt; human HD promoter	128	3 m	Inclusions in striatum; neuron loss in striatum	Rotarod deficit; clasping; gait abnormalities; circling behavior	2003 [137]
Mouse Hdh Q140	Replace mouse Htt exon 1 with expanded chimeric mouse/ human exon 1; mouse Hdh promoter	140	12 m	Nuclear and neuropil inclusions in striatum, cortex, nucleus accumbens, and olfactory tubercle	Increased locomotor activity and rearing at 1 month, followed by hypoactivity and gait abnormalities	2003 [138]
Transgenic Rat	A truncated Htt fragment; endogenous rat promoter	51	Adult onset	Neurological phenotypes, intracellular inclusions, striatal shrinkage	Progressive motor dysfunction	2003 [139]
Mouse BAC-HD	Full-length human Htt; human HD promoter	97	3 m	Synaptic dysfunction; cortical and striatal atrophy	Rotarod deficit	2008 [140]
Rhesus Macaque Monkey	Human HD exon 1 fused to GFP; Human polyubiquitin-C promoter	84	Birth to 1 week	Neuronal inclusions	Dystonia, chorea	2008 [141]
Rat BACHD	Human full-length HD genomic sequence; human HD promoter	97	Early onset	Cortical and striatal aggregates; neuropil aggregates appear earlier than inclusions; reduced dopamine receptor binding was detectable by in vivo imaging	Robust, early onset and progressive motor deficits and anxiety-related symptoms	2012 [142]

HD, human huntingtin gene; Hdh, mouse huntingtin gene; m, months of age; GAL4-UAS system, Transgenic flies expressing GAL4, a yeast transcriptional activator, are crossed with UAS-transgenic flies, carrying a gene of interest inserted downstream of the UAS (upstream activating sequence); YAC, yeast artificial chromosome; BAC, bacteria artificial chromosome; GFP, green fluorescent protein