ArticleProceedings of the National Academy of Sciences of the United States of America2012
Dysregulation of dopamine receptor D2 as a sensitive measure for Huntington disease pathology in model mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington's Disease Patients.Metabolites · 2022Article
- Cocaine Reduces the Neuronal Population While Upregulating Dopamine D2-Receptor-Expressing Neurons in Brain Reward Regions: Sex-Effects.Frontiers in pharmacology · 2021Article
- Early epigenomic and transcriptional changes reveal Elk-1 transcription factor as a therapeutic target in Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The TinyInternational journal of molecular sciences · 2018Review
- The adjustment of γ-aminobutyric acidNeural regeneration research · 2018Review
- Profilin reduces aggregation and phase separation of huntingtin N-terminal fragments by preferentially binding to soluble monomers and oligomers.The Journal of biological chemistry · 2018Article
- The ubiquitin conjugating enzyme Ube2W regulates solubility of the Huntington's disease protein, huntingtin.Neurobiology of disease · 2018Article
- Selective Vulnerability of Striatal D2 versus D1 Dopamine Receptor-Expressing Medium Spiny Neurons in HIV-1 Tat Transgenic Male Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Chromatin immunoprecipitation and gene expression analysis of neuronal subtypes after fluorescence activated cell sorting.Journal of neuroscience methods · 2016Article
- Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model.Journal of cellular and molecular medicine · 2015Article
- In Vivo Profiling Reveals a Competent Heat Shock Response in Adult Neurons: Implications for Neurodegenerative Disorders.PloS one · 2015Article
- Dopamine imbalance in Huntington's disease: a mechanism for the lack of behavioral flexibility.Frontiers in neuroscience · 2013Article
- Synthetic zinc finger repressors reduce mutant huntingtin expression in the brain of R6/2 mice.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Interrogation of brain miRNA and mRNA expression profiles reveals a molecular regulatory network that is perturbed by mutant huntingtin.Journal of neurochemistry · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The ability to quantitatively evaluate the impact of a potential therapeutic intervention for Huntington disease (HD) in animal models for the disease is a critical step in the pathway to development of an effective therapy for this devastating neurodegenerative disorder. We report here an approach that combines a cell-based assay's quantitative accuracy and direct relationship to molecular processes with the ability to directly monitor effects in HD model mouse neurons. To accomplish this goal, we have developed an accurate quantitative reporter assay for a transcript known to be down-regulated as an early consequence of mutant huntingtin expression. This system uses mouse strains carrying a GFP reporter for the expression of the dopamine receptor D2, expressed in the medium spiny neurons of the basal ganglion. This receptor consistently demonstrates reduced expression in patients and murine models, and the FACS-based assay gives a highly accurate and quantitative readout of this pathology in mouse neurons expressing mutant huntingtin. For four genetic models and one viral model, a highly reproducible time course of loss of reporter expression is observed. This quantitative measure of HD pathology can be used to measure the effects of HD therapeutics in small cohorts with high confidence. We further demonstrate that the introduction of an shRNA against the huntingtin transgene by virus can improve this pathological status in medium spiny neurons transduced with the construct. We believe this system can be of great utility in the validation of effective therapeutic interventions for HD.
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Registered trials
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