ArticleMolecular brain2012
A series of N-terminal epitope tagged Hdh knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal Huntingtin's polyglutamine stretch on CAG140 mouse model pathogenesis.
Article in Molecular brain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 18 citations in OpenAlex.
- Targeted quantification assays for DNA repair and handling proteins and interactions in Huntington's disease models.bioRxiv : the preprint server for biology · 2026Article
- Multi-epitope immunocapture of huntingtin reveals striatum-selective molecular signatures.Molecular systems biology · 2025Article
- Dynamics of huntingtin protein interactions in the striatum identifies candidate modifiers of Huntington disease.Cell systems · 2022Article
- Mutant Huntingtin Protein Interaction Map Implicates Dysregulation of Multiple Cellular Pathways in Neurodegeneration of Huntington's Disease.Journal of Huntington's disease · 2022Article
- Recent Microscopy Advances and the Applications to Huntington's Disease Research.Journal of Huntington's disease · 2022Review
- Identification of Full-Length Wild-Type and Mutant Huntingtin Interacting Proteins by Crosslinking Immunoprecipitation in Mice Brain Cortex.Journal of Huntington's disease · 2021Article
- Huntington's disease alters human neurodevelopment.Science (New York, N.Y.) · 2020Article
- CRISPR-Cas9-Mediated Epitope Tagging Provides Accurate and Versatile Assessment of Myocardin-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Huntingtin Is Required for Neural But Not Cardiac/Pancreatic Progenitor Differentiation of Mouse Embryonic Stem CellsFrontiers in cellular neuroscience · 2017Article
- Generation and Characterization of Knock-in Mouse Models Expressing Versions of Huntingtin with Either an N17 or a Combined PolyQ and Proline-Rich Region Deletion.Journal of Huntington's disease · 2017Article
- Huntington's Disease Protein Huntingtin Associates with its own mRNA.Journal of Huntington's disease · 2016Article
- Studying polyglutamine diseases in Drosophila.Experimental neurology · 2015Review
- Potential function for the Huntingtin protein as a scaffold for selective autophagy.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Huntingtin protein is essential for mitochondrial metabolism, bioenergetics and structure in murine embryonic stem cells.Developmental biology · 2014Article
- A large scale Huntingtin protein interaction network implicates Rho GTPase signaling pathways in Huntington disease.The Journal of biological chemistry · 2014Article
- Mapping the interactome of overexpressed RAF kinase inhibitor protein in a gastric cancer cell line.BMC cancer · 2013Article
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5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHuntington's disease (HD) is an autosomal dominant neurodegenerative disease that is caused by the expansion of a polyglutamine (polyQ) stretch within Huntingtin (htt), the protein product of the HD gene. Although studies in vitro have suggested that the mutant htt can act in a potentially dominant negative fashion by sequestering wild-type htt into insoluble protein aggregates, the role of the length of the normal htt polyQ stretch, and the adjacent proline-rich region (PRR) in modulating HD mouse model pathogenesis is currently unknown.
resultsWe describe the generation and characterization of a series of knock-in HD mouse models that express versions of the mouse HD gene (Hdh) encoding N-terminal hemaglutinin (HA) or 3xFlag epitope tagged full-length htt with different polyQ lengths (HA7Q-, 3xFlag7Q-, 3xFlag20Q-, and 3xFlag140Q-htt) and substitution of the adjacent mouse PRR with the human PRR (3xFlag20Q- and 3xFlag140Q-htt). Using co-immunoprecipitation and immunohistochemistry analyses, we detect no significant interaction between soluble full-length normal 7Q- htt and mutant (140Q) htt, but we do observe N-terminal fragments of epitope-tagged normal htt in mutant htt aggregates. When the sequences encoding normal mouse htt's polyQ stretch and PRR are replaced with non-pathogenic human sequence in mice also expressing 140Q-htt, aggregation foci within the striatum, and the mean size of htt inclusions are increased, along with an increase in striatal lipofuscin and gliosis.
conclusionIn mice, soluble full-length normal and mutant htt are predominantly monomeric. In heterozygous knock-in HD mouse models, substituting the normal mouse polyQ and PRR with normal human sequence can exacerbate some neuropathological phenotypes.
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