Evidence map›Paper›PMID 36577403›Full record

ArticleNeuron2023

Decreasing mutant ATXN1 nuclear localization improves a spectrum of SCA1-like phenotypes and brain region transcriptomic profiles.

Hillary P Handler, Lisa Duvick, Jason S Mitchell, Marija Cvetanovic, Molly Reighard, Alyssa Soles, Kathleen B Mather, Orion Rainwater, Shannah Serres, Tessa Nichols-Meade and 7 more

Open access · greenAbstract readComment
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

17 citing papers in PubMed, 29 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 1 country.

Hillary P HandlerInstitute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
Lisa DuvickInstitute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Jason S MitchellInstitute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Marija CvetanovicInstitute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
Molly ReighardInstitute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Alyssa SolesInstitute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
Kathleen B MatherInstitute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
Orion RainwaterInstitute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Shannah SerresInstitute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Tessa Nichols-MeadeInstitute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
Stephanie L CoffinProgram in Genetics & Genomics and Department of Molecular and Human Genetics, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
Yun YouMouse Genetics Laboratory, University of Minnesota, Minneapolis, MN 55455, USA.
Brian L RuisDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Brennon O'CallaghanInstitute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Christine HenzlerRISS Bioinformatics, Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Huda Y ZoghbiDepartments of Molecular and Human Genetics, Pediatrics, and Howard Hughes Medical Institute, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
Harry T OrrInstitute of Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: orrxx002@umn.edu.
University of Minnesota · USBaylor College of Medicine · USHoward Hughes Medical Institute · US

Funding

MOLECULAR STUDIES OF SPINOCEREBELLAR ATAXIA TYPE 1R01NS027699 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI HUDA Y ZOGHBI · 1989 to 2026
$8.8M
Molecular genetics of neurodegenerative pathogenic and protective pathways: The SCA1 perspectiveR35NS127248 · NINDS · UNIVERSITY OF MINNESOTA · PI Harry T. Orr · 2022 to 2026
$3.9M
MOLECULAR GENETICS OF THE SCA1 LOCUS ON CHROMOSOME 6PR01NS022920 · NINDS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI ORR, HARRY T. · 1986 to 2022
$3.2M
Etiology of cognitive decline in Spinocerebellar ataxia type 1R01NS109077 · NINDS · UNIVERSITY OF MINNESOTA · PI Marija Cvetanovic, TIMOTHY J EBNER · 2020 to 2026
$2.4M
NINDS NIH HHS R01 NS022920NINDS NIH HHS R01 NS027699NINDS NIH HHS R01 NS109077NINDS NIH HHS R35 NS127248
6 · The paper itself

Abstract

Spinocerebellar ataxia type 1 (SCA1) is a dominant trinucleotide repeat neurodegenerative disease characterized by motor dysfunction, cognitive impairment, and premature death. Degeneration of cerebellar Purkinje cells is a frequent and prominent pathological feature of SCA1. We previously showed that transport of ATXN1 to Purkinje cell nuclei is required for pathology, where mutant ATXN1 alters transcription. To examine the role of ATXN1 nuclear localization broadly in SCA1-like disease pathogenesis, CRISPR-Cas9 was used to develop a mouse with an amino acid alteration (K772T) in the nuclear localization sequence of the expanded ATXN1 protein. Characterization of these mice indicates that proper nuclear localization of mutant ATXN1 contributes to many disease-like phenotypes including motor dysfunction, cognitive deficits, and premature lethality. RNA sequencing analysis of genes with expression corrected to WT levels in Atxn1

Indexed as

Ataxin-1Spinocerebellar AtaxiasTranscriptomeAnimalsBrainCerebellumDisease Models, AnimalMiceMice, TransgenicNerve Tissue ProteinsPhenotypeProtein TransportPurkinje CellsAtaxin-1Atxn1 protein, mouseNerve Tissue Proteinsneurodegenerationnuclear localizationSCA1spinocerebellar ataxia type 1

Identifiers

PMID36577403
PMCPMC9957934
OpenAlexW4313252585

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Registered trials

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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.