Abstract：
:Rapid-onset dystonia with parkinsonism (RDP) or DYT12 dystonia is a rare form of primary, generalized dystonia. Patients do not present with any symptoms until triggered by a physiological stressor. Within days, patients will show both dystonia and parkinsonism. Mutations resulting in a loss of function in the ATP1A3 gene have been identified as the cause of RDP. ATP1A3 encodes the α3 subunit of the Na(+)/K(+)-ATPase, which is exclusively expressed in neurons and cardiac cells. We have previously created a line of mice harboring a point mutation of the Atp1a3 gene (mouse homolog of the human ATP1A3 gene) that results in a loss of function of the α3 subunit. The Atp1a3 mutant mice showed hyperactivity, spatial learning and memory deficits, and increased locomotion induced by methamphetamine. However, the full spectrum of the motor phenotype has not been characterized in the mutant mice and it is not known whether triggers such as restraint stress affect the motor phenotype. Here, we characterized the motor phenotype in normal heterozygous Atp1a3 mutant mice and heterozygous Atp1a3 mutant mice that have been exposed to a restraint stress. We found that this type of trigger induced significant deficits in motor coordination and balance in the mutant mice, characteristic of other genotypic dystonia mouse models. Furthermore, stressed mutant mice also had a decreased thermal sensitivity and alterations in monoamine metabolism. These results suggest that the Atp1a3 mutant mouse models several characteristics of RDP and further analysis of this mouse model will provide great insight into pathogenesis of RDP.
journal_name
Behav Brain Resjournal_title
Behavioural brain researchauthors
DeAndrade MP,Yokoi F,van Groen T,Lingrel JB,Li Ydoi
10.1016/j.bbr.2010.09.009subject
Has Abstractpub_date
2011-01-20 00:00:00pages
659-65issue
2eissn
0166-4328issn
1872-7549pii
S0166-4328(10)00632-7journal_volume
216pub_type
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journal_title：Behavioural brain research
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更新日期：2014-08-01 00:00:00
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更新日期：1996-01-01 00:00:00
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abstract：RATIONALE:Addiction is characterized by inflexible drug consumption: unpleasant consequences are accepted. Rat studies with several drugs proved that long-term voluntary intake induced abstinence-outlasting excessive and inflexible consumption. OBJECTIVE:Establishing a long-term model of oral self-administration of ni...
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