Evidence map›Paper›PMID 26804915›Full record

ArticleCell reports2016

A Mouse Model of X-linked Intellectual Disability Associated with Impaired Removal of Histone Methylation.

Shigeki Iwase, Emily Brookes, Saurabh Agarwal, Aimee I Badeaux, Hikaru Ito, Christina N Vallianatos, Giulio Srubek Tomassy, Tomas Kasza, Grace Lin, Andrew Thompson and 7 more

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

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
7.7field-weighted citation impact, top 2% 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

87 citing papers in PubMed, 147 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Chromatin modifiers in neurodevelopment.Frontiers in molecular neuroscience · 2025
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review

27 more citing papers are in PubMed but not listed here.

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

17 authors at 5 institutions in 1 country.

Shigeki IwaseDivision of Newborn Medicine, Boston Children's Hospital and Department of Cell Biology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Human Genetics, University of Michigan, 5815 Medical Science II, Ann Arbor, MI 48109, USA. Electronic address: siwase@umich.edu.
Emily BrookesDivision of Newborn Medicine, Boston Children's Hospital and Department of Cell Biology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Saurabh AgarwalDepartment of Human Genetics, University of Michigan, 5815 Medical Science II, Ann Arbor, MI 48109, USA.
Aimee I BadeauxDivision of Newborn Medicine, Boston Children's Hospital and Department of Cell Biology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Hikaru ItoDepartment of Integrative Physiology and Neuroscience, Washington State University, 1815 Ferdinand's Lane, Pullman, WA 99164, USA.
Christina N VallianatosDepartment of Human Genetics, University of Michigan, 5815 Medical Science II, Ann Arbor, MI 48109, USA.
Giulio Srubek TomassyDepartment of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Tomas KaszaDepartment of Human Genetics, University of Michigan, 5815 Medical Science II, Ann Arbor, MI 48109, USA.
Grace LinMolecular & Behavioral Neuroscience Institute and Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Andrew ThompsonDepartment of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Lei GuDivision of Newborn Medicine, Boston Children's Hospital and Department of Cell Biology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Kenneth Y KwanMolecular & Behavioral Neuroscience Institute and Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Chinfei ChenDepartment of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Maureen A SartorDepartment of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA.
Brian EganActive Motif Inc., Carlsbad, CA 92008, USA.
Jun XuDepartment of Integrative Physiology and Neuroscience, Washington State University, 1815 Ferdinand's Lane, Pullman, WA 99164, USA. Electronic address: junxu@vetmed.wsu.edu.
Yang ShiDivision of Newborn Medicine, Boston Children's Hospital and Department of Cell Biology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: yshi@hms.harvard.edu.
University of Michigan–Ann Arbor · USBoston Children's Hospital · USHarvard University · USWashington State University · USActive Motif (United States) · US

Funding

PREDOCTORAL TRAINING IN GENETICST32GM007544 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 1985 to 2022
$11.3M
Novel epigenetic mechanisms in neuronal development and cognitive functionR01MH096066 · NIMH · BOSTON CHILDREN'S HOSPITAL · PI ARLOTTA, PAOLA, POMEROY, SCOTT LOREN · 2012 to 2022
$6.1M
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI POMEROY, SCOTT LOREN · 2016 to 2020
$5.2M
Career Training in Reproductive BiologyT32HD079342 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Suzanne M MOENTER · 2014 to 2026
$2.3M
Neutralizing epigenomes in neurodevelopment disordersR01NS089896 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI IWASE, SHIGEKI · 2015 to 2019
$2.1M
NICHD NIH HHS T32 HD079342NICHD NIH HHS U54 HD090255NIGMS NIH HHS T32 GM007544NIGMS NIH HHS T32GM07544NIMH NIH HHS MH096066NIMH NIH HHS R01 MH096066NINDS NIH HHS NS089896NINDS NIH HHS R01 NS089896PHS HHS RN2-00905
6 · The paper itself

Abstract

Mutations in a number of chromatin modifiers are associated with human neurological disorders. KDM5C, a histone H3 lysine 4 di- and tri-methyl (H3K4me2/3)-specific demethylase, is frequently mutated in X-linked intellectual disability (XLID) patients. Here, we report that disruption of the mouse Kdm5c gene recapitulates adaptive and cognitive abnormalities observed in XLID, including impaired social behavior, memory deficits, and aggression. Kdm5c-knockout brains exhibit abnormal dendritic arborization, spine anomalies, and altered transcriptomes. In neurons, Kdm5c is recruited to promoters that harbor CpG islands decorated with high levels of H3K4me3, where it fine-tunes H3K4me3 levels. Kdm5c predominantly represses these genes, which include members of key pathways that regulate the development and function of neuronal circuitries. In summary, our mouse behavioral data strongly suggest that KDM5C mutations are causal to XLID. Furthermore, our findings suggest that loss of KDM5C function may impact gene expression in multiple regulatory pathways relevant to the clinical phenotypes.

Indexed as

Genes, X-LinkedAggressionAnimalsBrainCpG IslandsDendritic SpinesDisease Models, AnimalGene Expression RegulationHistone DemethylasesHistonesIntellectual DisabilityLysineMemoryMethylationMice, KnockoutOxidoreductases, N-DemethylatingHistone DemethylasesHistonesKdm5c protein, mouseLysineOxidoreductases, N-Demethylating

Identifiers

PMID26804915
PMCPMC4749408
OpenAlexW2259032664

What OpenQuestion holds

Textmetadata
LicenceTDM
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.