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Dopamine receptor and Gα(olf) expression in DYT1 dystonia mouse models during postnatal development.

Title: Dopamine receptor and Gα(olf) expression in DYT1 dystonia mouse models during postnatal development.
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Name(s): Zhang, Lin, author
McCarthy, Deirdre M, author
Sharma, Nutan, author
Bhide, Pradeep G, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2015-04-10
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: DYT1 dystonia is a heritable, early-onset generalized movement disorder caused by a GAG deletion (ΔGAG) in the DYT1 gene. Neuroimaging studies and studies using mouse models suggest that DYT1 dystonia is associated with dopamine imbalance. However, whether dopamine imbalance is key to DYT1 or other forms of dystonia continues to be debated. We used Dyt1 knock out (Dyt1 KO), Dyt1 ΔGAG knock-in (Dyt1 KI), and transgenic mice carrying one copy of the human DYT1 wild type allele (DYT1 hWT) or human ΔGAG mutant allele (DYT1 hMT). D1R, D2R, and Gα(olf) protein expression was analyzed by western blot in the frontal cortex, caudate-putamen and ventral midbrain in young adult (postnatal day 60; P60) male mice from all four lines; and in the frontal cortex and caudate putamen in juvenile (postnatal day 14; P14) male mice from the Dyt1 KI and KO lines. Dopamine receptor and Gα(olf) protein expression were significantly decreased in multiple brain regions of Dyt1 KI and Dyt1 KO mice and not significantly altered in the DYT1 hMT or DYT1 hWT mice at P60. The only significant change at P14 was a decrease in D1R expression in the caudate-putamen of the Dyt1 KO mice. We found significant decreases in key proteins in the dopaminergic system in multiple brain regions of Dyt1 KO and Dyt1 KI mouse lines at P60. Deletion of one copy of the Dyt1 gene (KO mice) produced the most pronounced effects. These data offer evidence that impaired dopamine receptor signaling may be an early and significant contributor to DYT1 dystonia pathophysiology.
Identifier: FSU_pmch_25860259 (IID), 10.1371/journal.pone.0123104 (DOI), PMC4393110 (PMCID), 25860259 (RID), 25860259 (EID), PONE-D-14-28479 (PII)
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393110.
Subject(s): Age Factors
Animals
Animals, Newborn
Brain/metabolism
Disease Models, Animal
Dystonia Musculorum Deformans/genetics
GTP-Binding Protein alpha Subunits/genetics
Gene Expression
Genotype
Humans
Male
Mice
Mice, Transgenic
Receptors, Dopamine/genetics
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_25860259
Owner Institution: FSU
Is Part Of: PloS one.
1932-6203
Issue: iss. 4, vol. 10

Choose the citation style.
Zhang, L., McCarthy, D. M., Sharma, N., & Bhide, P. G. (2015). Dopamine receptor and Gα(olf) expression in DYT1 dystonia mouse models during postnatal development. Plos One. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_25860259