Detection of HTTex1p by western blot and immunostaining of HD human and mouse brain using neo-epitope antibody P90 highlights impact of CAG repeat expansion on its size, solubility, and response to MSH3 silencing | Semantic Scholar (2025)

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@article{Sapp2025DetectionOH, title={Detection of HTTex1p by western blot and immunostaining of HD human and mouse brain using neo-epitope antibody P90 highlights impact of CAG repeat expansion on its size, solubility, and response to MSH3 silencing}, author={Ellen Sapp and Adel Boudi and Andrew Iwanowicz and Jillian Belgrad and Rachael Miller and Daniel O’Reilly and Ken Yamada and Yunping Deng and Marion Joni and Xueyi Li and Kimberly B. Kegel-Gleason and Anastasia Khvorova and Anton Reiner and Neil Aronin and Marian Difiglia}, journal={bioRxiv}, year={2025}, url={https://api.semanticscholar.org/CorpusID:275335096}}
  • E. Sapp, Adel Boudi, M. Difiglia
  • Published in bioRxiv 1 January 2025
  • Medicine, Biology

P90 antibodies can be used in western blot assays and immunostaining to track and quantify HTTex1p levels, subcellular localization, and solubility and show that the effects of curbing CAG repeat expansion was quantifiable.

41 References

Huntingtin HTT1a is generated in a CAG repeat-length-dependent manner in human tissues
    Franziska HoschekJulia Natan Andreas Neueder

    Medicine, Biology

    Molecular medicine

  • 2024

Background The disease-causing mutation in Huntington disease (HD) is a CAG trinucleotide expansion in the huntingtin (HTT) gene. The mutated CAG tract results in the production of a small RNA,

  • 6
  • PDF
The pathogenic exon 1 HTT protein is produced by incomplete splicing in Huntington’s disease patients
    Andreas NeuederC. Landles G. Bates

    Medicine, Biology

    Scientific Reports

  • 2017

It is found that the HTTexon1 mRNA is present in fibroblasts from juvenile HD patients and can also be readily detected in the sensory motor cortex, hippocampus and cerebellum of post-mortem brains from HD individuals, particularly in those with early onset disease.

  • 178
  • Highly Influential
  • PDF
Alternative processing of human HTT mRNA with implications for Huntington’s disease therapeutics
    Sandra FieńkoC. Landles G. Bates

    Medicine, Biology

    Brain : a journal of neurology

  • 2022

The levels of exon 1 HTT in YAC128 mice, correlated with HTT aggregation, supportive of the hypothesis that exon 2 HTT initiates the aggregation process, and of the need for agents targeting HTT1a are developed.

  • 19
  • Highly Influential
  • [PDF]
Protein changes in synaptosomes of Huntington's disease knock-in mice are dependent on age and brain region
    E. SappConnor Seeley Kimberly B. Kegel-Gleason

    Biology, Medicine

    Neurobiology of Disease

  • 2020
  • 27
  • PDF
Native Mutant Huntingtin in Human Brain
    E. SappA. Valencia M. Difiglia

    Biology, Medicine

    The Journal of Biological Chemistry

  • 2012

Native full-length mutant htt in embryonic HD140Q/140Q mouse primary neurons was intact during cell death and when cell lysates were exposed to denaturants before BNP, indicating a property of native htt to resist protease cleavage.

  • 28
  • PDF
Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease
    K. SathasivamAndreas Neueder G. Bates

    Medicine, Biology

    Proceedings of the National Academy of Sciences

  • 2013

It is shown that CAG repeat length–dependent aberrant splicing of exon 1 HTT results in a short polyadenylated mRNA that is translated into an exon 2 HTT protein, which provides a mechanistic basis for the molecular pathogenesis of HD.

  • 453
  • Highly Influential
  • PDF
Comparison of mHTT Antibodies in Huntington’s Disease Mouse Models Reveal Specific Binding Profiles and Steady-State Ubiquitin Levels with Disease Development
    Z. Bayram-WestonL. JonesS. DunnettS. Brooks

    Biology, Medicine

    PloS one

  • 2016

The data indicate that generalisations across models regarding the quantification of aggregations may not be valid and that mHTT antibody binding is unique to the mouse model and sensitive to changes in inclusion development.

Proteolysis of Mutant Huntingtin Produces an Exon 1 Fragment That Accumulates as an Aggregated Protein in Neuronal Nuclei in Huntington Disease*
    C. LandlesK. Sathasivam G. Bates

    Medicine, Biology

    The Journal of Biological Chemistry

  • 2010

It is demonstrated that the smallest fragment is an exon 1 huntingtin protein, known to contain a potent nuclear export signal that accumulate in neuronal nuclei in the form of a detergent insoluble complex, visualized as diffuse granular nuclear staining in tissue sections.

  • 303
  • Highly Influential
  • PDF
Subcellular Localization And Formation Of Huntingtin Aggregates Correlates With Symptom Onset And Progression In A Huntington’S Disease Model
    C. LandlesRebecca E Milton G. Bates

    Medicine, Biology

    Brain communications

  • 2020

The R6/2 mouse model is used to investigate the molecular and behavioural consequences of expressing exon 1 HTT with 90 CAGs, a mutation that causes juvenile Huntington’s disease, and it is shown that nuclear aggregation occurred earlier in R 6/2(CAG)90 mice and that this correlated with the onset of transcriptional dysregulation.

  • 33
  • Highly Influential
  • [PDF]
Early detection of exon 1 huntingtin aggregation in zQ175 brains by molecular and histological approaches
    Edward J. SmithK. Sathasivam G. Bates

    Medicine, Biology

    Brain communications

  • 2023

The hypothesis that exon 1 huntingtin initiates the aggregation process in knock-in mouse models and pave the way for a detailed analysis of huntingtin aggregation in response to huntingtin-lowering treatments is supported.

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