Table 2.

Murine DYT1 models

Model	Molecular Construct	Morphology	Behavior	Neurochemistry
DYT1 transgenic (Shashidharan et al., 2005)	7.1 kb fragment from the pNSE-Ex4 vector containing the neuronspecific enolase promoter, human mutant (ΔGAG) torsinA-cDNA and SV40 polyA signal	ubiquitin- and torsinA-IR perinuclear aggregates and/or inclusion in the pedunculopontine nucleus, pons & periaqueductal gray	40% of transgenic mice from each line displayed dystonic movements of the limbs with self-clasping, circling behavior, & hyperactivity	↓ striatal DA in transgenic animals that exhibited an abnormal behavioral phenotype, ↓ striatal DOPAC/DA ratio in all transgenic mice
DYT1 transgenic (Sharma et al., 2005)	human wildtype (hWT) or mutant (ΔGAG) torsinA-cDNAs were inserted into pcDNA3.1 under the human cytomegalovirus immediate early promoter.	no torsinA-positive inclusions or increased staining around the nuclear envelope (NE)	reduced ability to learn motor skills in an accelerating rotarod paradigm	↓ amphetamine-induced striatal extracellular DA levels
DYT1 knock-in (Dang et al., 2005)	Exon 5 in the targeting vector construct carries a GAA deletion at codon 302. The PGKNeoSTOP cassette with a false translation signal, splice donor site, and an additional poly(A) tail was inserted into intron 4.	ubiquitin- and torsinA- containing aggregates in pontine nuclei of male DTY1 knock-in mice	deficient performance on the beam-walking test, open-field hyperactivity	↓ striatal HVA
DYT1 knock-out (Goodchild et al., 2005)	Exons 2-4 of Tor1a were replaced by a cassette containing Neo and IRES-tau LacZ sequences	vesicles within the neuronal NE that appear to derive from the inner nuclear membrane
DYT1 knock-in (Goodchild et al., 2005)	Exon 5 in the targeting construct carries a GAG deletion. Neo cassettewas inserted into intron 4 of Tor1a.	homozygotes exhibit vesicles within the neuronal NE that appear to derive from the inner nuclear membrane
TOR1A knock-down (Dang et al., 2006)	PGKNeoSTOP cassette with a false translation signal, splice donor site, and an additional poly(A) tail was inserted into intron 4 of Tor1a and recombination occurred 5′ to an Exon 5 GAA deletion		horizontal hyperactivity, ↑ slips on a beam-walking test	↓ striatal DOPAC
DYT1 transgenic (Grundmann et al., 2007)	human wild-type (hWT) and mutant (hΔGAG) torsinA-cDNAs were inserted into pBluescript II SK-vector under the 3.4 kb fragment of the murine prion protein promoter and tagged C-terminally with V5-His	inclusion-like formation in brainstem nuclei, torsinA-IR localized to the NE, and NE abnormalities in both hWT and hΔGAG mice	hWT mice: hypoactivity, short stride length, prolonged traversal times on beam walking hΔGAG mice: hyperactive, defects on rotarod testing	hWT mice: ↓ striatal DA, 5-HT and 5-HIAA; ↓ brainstem HVA hΔGAG mice: ↑ brainstem DOPAC, 5-HT and 5-HIAA