PMID- 21931745
OWN - NLM
STAT- MEDLINE
DCOM- 20120608
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 9
DP  - 2011
TI  - Motor deficits and decreased striatal dopamine receptor 2 binding activity in the 
      striatum-specific Dyt1 conditional knockout mice.
PG  - e24539
LID - 10.1371/journal.pone.0024539 [doi]
LID - e24539
AB  - DYT1 early-onset generalized dystonia is a hyperkinetic movement disorder caused 
      by mutations in DYT1 (TOR1A), which codes for torsinA. Recently, significant 
      progress has been made in studying pathophysiology of DYT1 dystonia using 
      targeted mouse models. Dyt1 DeltaGAG heterozygous knock-in (KI) and Dyt1 knock-down 
      (KD) mice exhibit motor deficits and alterations of striatal dopamine 
      metabolisms, while Dyt1 knockout (KO) and Dyt1 DeltaGAG homozygous KI mice show 
      abnormal nuclear envelopes and neonatal lethality. However, it has not been clear 
      whether motor deficits and striatal abnormality are caused by Dyt1 mutation in 
      the striatum itself or the end results of abnormal signals from other brain 
      regions. To identify the brain region that contributes to these phenotypes, we 
      made a striatum-specific Dyt1 conditional knockout (Dyt1 sKO) mouse. Dyt1 sKO 
      mice exhibited motor deficits and reduced striatal dopamine receptor 2 (D2R) 
      binding activity, whereas they did not exhibit significant alteration of striatal 
      monoamine contents. Furthermore, we also found normal nuclear envelope structure 
      in striatal medium spiny neurons (MSNs) of an adult Dyt1 sKO mouse and cerebral 
      cortical neurons in cerebral cortex-specific Dyt1 conditional knockout (Dyt1 cKO) 
      mice. The results suggest that the loss of striatal torsinA alone is sufficient 
      to produce motor deficits, and that this effect may be mediated, at least in 
      part, through changes in D2R function in the basal ganglia circuit.
FAU - Yokoi, Fumiaki
AU  - Yokoi F
AD  - Department of Neurology, College of Medicine, University of Florida, Gainesville, 
      Florida, United States of America.
FAU - Dang, Mai Tu
AU  - Dang MT
FAU - Li, Jianyong
AU  - Li J
FAU - Standaert, David G
AU  - Standaert DG
FAU - Li, Yuqing
AU  - Li Y
LA  - eng
GR  - NS37409/NS/NINDS NIH HHS/United States
GR  - ,NS57098/NS/NINDS NIH HHS/United States
GR  - NS47692/NS/NINDS NIH HHS/United States
GR  - NS65273/NS/NINDS NIH HHS/United States
GR  - R21 NS065273/NS/NINDS NIH HHS/United States
GR  - NS74423/NS/NINDS NIH HHS/United States
GR  - R21 NS047692/NS/NINDS NIH HHS/United States
GR  - NS47466/NS/NINDS NIH HHS/United States
GR  - P01 NS037409/NS/NINDS NIH HHS/United States
GR  - R01 NS054246/NS/NINDS NIH HHS/United States
GR  - P30 NS047466/NS/NINDS NIH HHS/United States
GR  - P50 NS037409/NS/NINDS NIH HHS/United States
GR  - P30 NS057098/NS/NINDS NIH HHS/United States
GR  - NS72782/NS/NINDS NIH HHS/United States
GR  - NS54246/NS/NINDS NIH HHS/United States
GR  - R03 NS074423/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110912
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Dyt1 protein, mouse)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (stromal cell-derived receptor 2, mouse)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Brain/metabolism
MH  - Cell Nucleus/metabolism
MH  - Crosses, Genetic
MH  - Gene Deletion
MH  - Homozygote
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Molecular Chaperones/*genetics
MH  - Motor Skills
MH  - Mutation
MH  - Phenotype
MH  - Receptors, Cell Surface/*genetics
PMC - PMC3171455
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/09/21 06:00
MHDA- 2012/06/09 06:00
PMCR- 2011/09/12
CRDT- 2011/09/21 06:00
PHST- 2011/05/04 00:00 [received]
PHST- 2011/08/12 00:00 [accepted]
PHST- 2011/09/21 06:00 [entrez]
PHST- 2011/09/21 06:00 [pubmed]
PHST- 2012/06/09 06:00 [medline]
PHST- 2011/09/12 00:00 [pmc-release]
AID - PONE-D-11-07920 [pii]
AID - 10.1371/journal.pone.0024539 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(9):e24539. doi: 10.1371/journal.pone.0024539. Epub 2011 Sep 12.