ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Lentiviral-mediated delivery of mutant huntingtin in the striatum of rats induces a selective neuropathology modulated by polyglutamine repeat size, huntingtin expression levels, and protein length.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 217 citations in OpenAlex.
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- Selective, broad-spectrum antiviral photodynamic disinfection with dicationic imidazolyl chlorin photosensitizers.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2023Article
- The stress granule protein G3BP1 alleviates spinocerebellar ataxia-associated deficits.Brain : a journal of neurology · 2023Article
- The Role of the Thioredoxin System in Brain Diseases.Antioxidants (Basel, Switzerland) · 2022Review
- ULK overexpression mitigates motor deficits and neuropathology in mouse models of Machado-Joseph disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Microarray profiling of hypothalamic gene expression changes in Huntington's disease mouse models.Frontiers in neuroscience · 2022Article
- Autophagy in Spinocerebellar ataxia type 2, a dysregulated pathway, and a target for therapy.Cell death & disease · 2021Article
- Transplantation of human embryonic stem cells alleviates motor dysfunction in AAV2-Htt171-82Q transfected rat model of Huntington's disease.Stem cell research & therapy · 2021Article
- The emerging roles of long non-coding RNAs in polyglutamine diseases.Journal of cellular and molecular medicine · 2021Review
- Gene targeting techniques for Huntington's disease.Ageing research reviews · 2021Review
- Impact of differential and time-dependent autophagy activation on therapeutic efficacy in a model of Huntington disease.Autophagy · 2021Article
- Mutant Huntingtin Is Cleared from the Brain via Active Mechanisms in Huntington Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- An Optimization of AAV-82Q-Delivered Rat Model of Huntington's Disease.Journal of Korean Neurosurgical Society · 2020Article
- Effects of flanking sequences and cellular context on subcellular behavior and pathology of mutant HTT.Human molecular genetics · 2020Article
- The striatal kinase DCLK3 produces neuroprotection against mutant huntingtin.Brain : a journal of neurology · 2018Article
- Translation of MicroRNA-Based Huntingtin-Lowering Therapies from Preclinical Studies to the Clinic.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Review
- Transcriptional Regulation of the Huntingtin Gene.Journal of Huntington's disease · 2018Review
- AAV5-miHTT gene therapy demonstrates suppression of mutant huntingtin aggregation and neuronal dysfunction in a rat model of Huntington's disease.Gene therapy · 2017Article
- Preclinical Evaluation of a Lentiviral Vector for Huntingtin Silencing.Molecular therapy. Methods & clinical development · 2017Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
A new strategy based on lentiviral-mediated delivery of mutant huntingtin (htt) was used to create a genetic model of Huntington's disease (HD) in rats and to assess the relative contribution of polyglutamine (CAG) repeat size, htt expression levels, and protein length on the onset and specificity of the pathology. Lentiviral vectors coding for the first 171, 853, and 1520 amino acids of wild-type (19 CAG) or mutant htt (44, 66, and 82 CAG) driven by either the phosphoglycerate kinase 1 (PGK) or the cytomegalovirus (CMV) promoters were injected in rat striatum. A progressive pathology characterized by sequential appearance of ubiquitinated htt aggregates, loss of dopamine- and cAMP-regulated phosphoprotein of 32 kDa staining, and cell death was observed over 6 months with mutant htt. Earlier onset and more severe pathology occurred with shorter fragments, longer CAG repeats, and higher expression levels. Interestingly, the aggregates were predominantly located in the nucleus of PGK-htt171-injected rats, whereas they were present in both the nucleus and processes of CMV-htt171-injected animals expressing lower transgene levels. Finally, a selective sparing of interneurons was observed in animals injected with vectors expressing mutant htt. These data demonstrate that lentiviral-mediated expression of mutant htt provides a robust in vivo genetic model for selective neural degeneration that will facilitate future studies on the pathogenesis of cell death and experimental therapeutics for HD.
Indexed as
Identifiers
11978824PMC6758353W2137023268What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.