Evidence map›Paper›PMID 31282030›Full record

ArticleJournal of neuroscience research2019

Phenotype onset in Huntington's disease knock-in mice is correlated with the incomplete splicing of the mutant huntingtin gene.

Nicholas R Franich, Miriam A Hickey, Chunni Zhu, Georgina F Osborne, Nadira Ali, Tiffany Chu, Nicholas H Bove, Vincent Lemesre, Renata P Lerner, Scott O Zeitlin and 5 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroscience research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
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  4. Prevention of ubiquitination at K6 and K9 in mutant huntingtin exacerbates disease pathology in a knock-in mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  5. Review
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  8. Article
  9. Review
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  12. Huntingtin Interacting Proteins and Pathological Implications.International journal of molecular sciences · 2023
    Review
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  14. Article
  15. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 3 countries.

Nicholas R FranichDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Miriam A HickeyDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Chunni ZhuDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Georgina F OsborneHuntington's Disease Centre, Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK.
Nadira AliHuntington's Disease Centre, Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK.
Tiffany ChuDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Nicholas H BoveDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Vincent LemesreDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Renata P LernerDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Scott O ZeitlinDepartment of Neuroscience, University of Virginia School of Medicine, Charlottesville, Virginia.
David HowlandCHDI Management/CHDI Foundation Inc., New York, New York.
Andreas NeuederHuntington's Disease Centre, Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK.
Christian LandlesHuntington's Disease Centre, Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK.
Gillian P BatesHuntington's Disease Centre, Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK.ORCID 0000-0002-4041-6305
Marie-Francoise ChesseletDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
University of California, Los Angeles · USUK Dementia Research Institute · GBCHDI Foundation · USUniversity of Virginia · US

Funding

Huntingtin proline-rich region modulation of Huntington's disease pathogenesisR01NS077926 · NINDS · UNIVERSITY OF VIRGINIA · PI ZEITLIN, SCOTT · 2014 to 2018
$1.7M
Modeling the effects of reducing huntingtin and Hdh alternative splicing in miceR01NS090914 · NINDS · UNIVERSITY OF VIRGINIA · PI ZEITLIN, SCOTT · 2015 to 2018
$1.4M
Medical Research Council MR/L003627/1Medical Research Council MR/L003627/2NINDS NIH HHS R01 NS077926NINDS NIH HHS R01 NS090914
6 · The paper itself

Abstract

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expanded CAG repeat within the huntingtin (HTT) gene. The Q140 and HdhQ150 knock-in HD mouse models were generated such that HdhQ150 mice have an expanded CAG repeat inserted into the mouse Htt gene, whereas in the Q140s, mouse exon 1 Htt was replaced with a mutated version of human exon 1. By standardizing mouse strain background, breeding to homozygosity and employing sensitive behavioral tests, we demonstrate that the onset of behavioral phenotypes occurs earlier in the Q140 than the HdhQ150 knock-in mouse models and that huntingtin (HTT) aggregation appears earlier in the striata of Q140 mice. We have previously found that the incomplete splicing of mutant HTT from exon 1 to exon 2 results in the production of a small polyadenylated transcript that encodes the highly pathogenic mutant HTT exon 1 protein. In this report, we have identified a functional consequence of the sequence differences between these two models at the RNA level, in that the level of incomplete splicing, and of the mutant exon 1 HTT protein, are greater in the brains of Q140 mice. While differences in the human and mouse exon 1 HTT proteins (e.g., proline rich sequences) could also contribute to the phenotypic differences, our data indicate that the incomplete splicing of HTT and approaches to lower the levels of the exon 1 HTT transcript should be pursued as therapeutic targets.

Indexed as

Disease Models, AnimalAnimalsBehavior, AnimalBrainFemaleGene Knock-In TechniquesHuntingtin ProteinHuntington DiseaseMaleMice, Inbred C57BLMice, TransgenicMutationPhenotypeHTT protein, humanHuntingtin Proteinhuntingtinhuntingtin aggregationhuntingtin splicingmouse behaviormouse modelsneurodegenerative diseasepathologypolyglutamineRRID:AB_528290RRID:AB_528297RRID:AB_532270

Identifiers

PMID31282030
PMCPMC6801054
OpenAlexW2962591442

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.