ArticleJournal of neurophysiology2012
A critical window of CAG repeat-length correlates with phenotype severity in the R6/2 mouse model of Huntington's disease.
Article in Journal of neurophysiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Advances and Challenges in Gene Therapy for Neurodegenerative Diseases: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Fingolimod Effects on Motor Function and BDNF-TrkB Signaling in a Huntington's Mouse Model Are Disease-Stage-Dependent.International journal of molecular sciences · 2026Article
- Development of cognitive, motor, metabolic, and mutant huntingtin aggregation in the zQ175 mouse model of Huntington's disease.Scientific reports · 2025Article
- CMS121 Partially Attenuates Disease Progression in Mouse Models of Huntington's Disease.Molecular neurobiology · 2024Article
- Replication Protein A, the Main Eukaryotic Single-Stranded DNA Binding Protein, a Focal Point in Cellular DNA Metabolism.International journal of molecular sciences · 2024Review
- Magnetic Resonance Imaging to Detect Structural Brain Changes in Huntington's Disease: A Review of Data from Mouse Models.Journal of Huntington's disease · 2024Review
- Rodent Models of Huntington's Disease: An Overview.Biomedicines · 2023Review
- Article
- Involvement of CRMP2 in Regulation of Mitochondrial Morphology and Motility in Huntington's Disease.Cells · 2021Article
- What is the Pathogenic CAG Expansion Length in Huntington's Disease?Journal of Huntington's disease · 2021Review
- Quantification of Huntington's Disease Related Markers in the R6/2 Mouse Model.Frontiers in molecular neuroscience · 2020Article
- Subcellular Localization And Formation Of Huntingtin Aggregates Correlates With Symptom Onset And Progression In A Huntington'S Disease Model.Brain communications · 2020Article
- Developmental origins of cortical hyperexcitability in Huntington's disease: Review and new observations.Journal of neuroscience research · 2019Review
- CRISPR-Cas9-Mediated Genome Editing Increases Lifespan and Improves Motor Deficits in a Huntington's Disease Mouse Model.Molecular therapy. Nucleic acids · 2019Article
- Cortical circuit alterations precede motor impairments in Huntington's disease mice.Scientific reports · 2019Article
- Normalizing glucocorticoid levels attenuates metabolic and neuropathological symptoms in the R6/2 mouse model of huntington's disease.Neurobiology of disease · 2019Article
- GLP-1 Analogue Liraglutide Attenuates Mutant Huntingtin-Induced Neurotoxicity by Restoration of Neuronal Insulin Signaling.International journal of molecular sciences · 2018Article
- Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice.Stem cell reports · 2018Article
- A novel ex vivo Huntington's disease model for studying GABAergic neurons and cell grafts by laser microdissection.PloS one · 2018Article
- Motor phenotype is not associated with vascular dysfunction in symptomatic Huntington's disease transgenic R6/2 (160 CAG) mice.Scientific reports · 2017Article
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Authors and funding
11 authors.
Funding
Abstract
The R6/2 mouse is the most frequently used model for experimental and preclinical drug trials in Huntington's disease (HD). When the R6/2 mouse was first developed, it carried exon 1 of the huntingtin gene with ~150 cytosine-adenine-guanine (CAG) repeats. The model presented with a rapid and aggressive phenotype that shared many features with the human condition and was particularly similar to juvenile HD. However, instability in the CAG repeat length due to different breeding practices has led to both decreases and increases in average CAG repeat lengths among colonies. Given the inverse relationship in human HD between CAG repeat length and age at onset and to a degree, the direct relationship with severity of disease, we have investigated the effect of altered CAG repeat length. Four lines, carrying ~110, ~160, ~210, and ~310 CAG repeats, were examined using a battery of tests designed to assess the basic R6/2 phenotype. These included electrophysiological properties of striatal medium-sized spiny neurons, motor activity, inclusion formation, and protein expression. The results showed an unpredicted, inverted "U-shaped" relationship between CAG repeat length and phenotype; increasing the CAG repeat length from 110 to 160 exacerbated the R6/2 phenotype, whereas further increases to 210 and 310 CAG repeats greatly ameliorated the phenotype. These findings demonstrate that the expected relationship between CAG repeat length and disease severity observed in humans is lost in the R6/2 mouse model and highlight the importance of CAG repeat-length determination in preclinical drug trials that use this model.
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