Evidence map›Paper›PMID 38461417›Full record

ArticleCell reports2024

Deletion of Pax1 scoliosis-associated regulatory elements leads to a female-biased tail abnormality.

Aki Ushiki, Rory R Sheng, Yichi Zhang, Jingjing Zhao, Mai Nobuhara, Elizabeth Murray, Xin Ruan, Jonathan J Rios, Carol A Wise, Nadav Ahituv

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

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
4.6field-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

9 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Deletion of aJOR spine · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Aki UshikiDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA.
Rory R ShengDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA.
Yichi ZhangDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA; School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Jingjing ZhaoDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA.
Mai NobuharaDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA.
Elizabeth MurrayDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA.
Xin RuanDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA.
Jonathan J RiosCenter for Translational Research, Scottish Rite for Children, Dallas, TX 75390, USA; Department of Orthopedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Carol A WiseCenter for Translational Research, Scottish Rite for Children, Dallas, TX 75390, USA; Department of Orthopedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Nadav AhituvDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: nadav.ahituv@ucsf.edu.
University of California, San Francisco · USTexas Scottish Rite Hospital for Children · US

Funding

Non-coding/epigenetic regulationP01HD084387 · NICHD · UT SOUTHWESTERN MEDICAL CENTER · PI Nadav Ahituv, LILIANNA SOLNICAKREZEL · 2016 to 2026
$14.2M
NICHD NIH HHS P01 HD084387
6 · The paper itself

Abstract

Adolescent idiopathic scoliosis (AIS), a sideways curvature of the spine, is sexually dimorphic, with increased incidence in females. A genome-wide association study identified a female-specific AIS susceptibility locus near the PAX1 gene. Here, we use mouse enhancer assays, three mouse enhancer knockouts, and subsequent phenotypic analyses to characterize this region. Using mouse enhancer assays, we characterize a sequence, PEC7, which overlaps the AIS-associated variant, and find it to be active in the tail tip and intervertebral disc. Removal of PEC7 or Xe1, a known sclerotome enhancer nearby, or deletion of both sequences lead to a kinky tail phenotype only in the Xe1 and combined (Xe1+PEC7) knockouts, with only the latter showing a female sex dimorphic phenotype. Extensive phenotypic characterization of these mouse lines implicates several differentially expressed genes and estrogen signaling in the sex dimorphic bias. In summary, our work functionally characterizes an AIS-associated locus and dissects the mechanism for its sexual dimorphism.

Indexed as

ScoliosisAnimalsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyMicePaired Box Transcription FactorsTailTranscription FactorsPaired Box Transcription FactorsPAX1 transcription factorTranscription FactorsAISCP: Molecular biologyenhancerGWASPax1scoliosissexual dimorphism

Identifiers

PMID38461417
PMCPMC11005513
OpenAlexW4392578347

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.