Table 3. Transgenic DYT1 dystonia rodent models.
Promoter | Microdialysis | Monoamines | Locomotion | Rotarod | Beam Walking | Gait Analysis | Neuronal phenotype | Additional findings |
---|---|---|---|---|---|---|---|---|
Rat neuron-specific
enolase |
NA | ↓ DA in striatum (mice with affected phenotype) 64 ↓ DOPAC/DA in striatum (mice with unaffected and affected phenotype) (1.5months)64 |
Self-clasping, hyperkinesia, circling (mice with affected phenotype (1.5-months)64 ↓ Rearing (3 months)65 |
Not affected (3,6,9,12 months)65 |
NA | ↓ Forelimb and hind limb stride length ( 9 months)65 |
Perinuclear inclusions for ubiquitin and TorsinA in PPN and PAG64 |
Transgene expression lost after repeated breeding65 |
Human
cytomegalovirus (CMV) |
Not affected DA at baseline in striatum68 ↓ DA by AMPH in striatum (6months- male)68 ↓ DAT activity in striatum (6- months-male)69 |
Not affectedin striatum (6 months-male)68 ↑ DOPAC/DA and HVA/DA in striatum (3-4months- male)67 |
Not affected (9months-male)66 ↓ Basal locomotion activity and by AMPH (6months- male)69 |
↓ Motor learning (9 months- male)66 Not affected (3-4 months male)67 |
↑ Transversal time and slips (3-4months-male)67 |
↑ Hind base width (3-4 months- male)67 |
No torsinA or ubiquitin inclusions in striatum (male)66 No torsinA or ubiquitin inclusions No bleb formation in nuclear envelope (male)67 |
Abnormal response to D2 dopamine receptor stimulation of Chls (9 months)72 Normal DAT, VMAT2, striatal DA receptors density (6 months-female)68 Impaired LTD and SD in medium spiny neurons70 ↑ Striatal acetylcholinesterase activity (~2months)70 Altered GABAergic function in striatum (~2 months)75 ↓ D2R, ↓ RGS9 in striatum (~2 months)74 ↓Pause response by thalamic stimulation in Chls (male)71 |
Murine prion | NA | htorsinAΔE mice: ↑ DOPAC, 5-HT, and 5-HIAA in brain stem htorsinA mice: ↓DA, 5-HT and 5-HIAA in striatum (5 months- male/female)77 |
htorsinAΔE mice: ↑ Activity (6months- male/female)77 htorsinA mice: ↓ Activity |
htorsinAΔE: ↓ Latency to fall, ↓ Learning (6months- ale/female)77 htorsinA mice: Not affected |
htorsinAΔE: Not affected (6months- male/female)77 htorsinA mice: ↑ Transversal time |
htorsinAΔE: Not affected (6months- male/female)77 htorsinA mice: ↓ Mean stride length for forelimbs and hind limbs |
htorsinAΔE and htorsinA: torsinA or ubiquitin inclusions mainly in brainstem, nuclear envelope disruption in brainstem and striatum (1.5months male)77 |
Altered motor circuits integrity by diffusion tensor imaging in cortex, striatum, cerebellum (5months -male)77 |
Tor1A promoter
(rat model) |
NA | NA | NA | ↓ Latency to fall at training sessions ( 2 months - male)78 |
↑ Transversal time 3,5 cm round beam (2months-male)78 |
↑ Variation of step length (hind limb) (11months male- )78 |
Abnormal protein localization of human torsinAΔE to nuclear envelope (cortex, hippocampus, striatum, olfactory bulb, substantia nigra)(2 months- male)78 Altered nuclear envelope structure in cortex and striatum ( 3 months- male)78 |
Limb grasping and clasping (11 months-male) Impaired LTD and SD in medium spiny neurons (8-12 weeks old-male)78 |
Human TH promoter
fragment (transgene expression in dopaminergic neurons of midbrain) |
TH- htorsinAΔE: Not affected DA at baseline and ↓ DA by cocaine in striatum (male) TH-htorsinA mice: ↑ DA release by cocaine in striatum76 |
TH- htorsinAΔEmice: Normal DA and DOPAC in striatum TH-hTorsinA mice: ↓ DA and ↓ DOPAC in striatum (2.5 months-female)76 |
TH- htorsinAΔE mice: Normal baseline locomotion TH-htorsinA mice: ↓ Baseline locomotion (4-10months male)76 |
Not affected (2,4,6 months male/female)76 |
TH- htorsinAΔE mice: ↑ Transversal time and slips male/female)76 |
NA | NA |
Abbreviations: 5-HIAA (5-hydroxyindoleacetic acid), 5-HT (5-hydroxytryptophan), AMPH (amphetamine), Chls (cholinergic interneurons), DA (dopamine), DAT (DA transporter), DOPAC (3, 4-dihydroxyphenylacetic acid), D2R ( dopamine receptor type 2), HVA (homovanillic acid), htorsinAΔE (human wild-type torsinA), htorsinAAE (human mutant torsinA with a GAG deletion), LTD (long-term depression, NA (Not analyzed), PPN (pedunculopontine nucleus), PAG (periaqueductal gray), RGS9 (Regulator of G-protein signaling 9), SD (synaptic depotentiation),TH (tyrosine hydroxylase), VMAT2 (vesicular monoamine transporter).