Evidence map›Paper›PMID 38881329›Full record

ArticleDisease models & mechanisms2024

An Irak1-Mecp2 tandem duplication mouse model for the study of MECP2 duplication syndrome.

Eleonora Maino, Ori Scott, Samar Z Rizvi, Wing Suen Chan, Shagana Visuvanathan, Youssif Ben Zablah, Hongbin Li, Ameet S Sengar, Michael W Salter, Zhengping Jia and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Disease models & mechanisms, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
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

14 authors.

Eleonora MainoProgram in Genetics and Genome Biology, the Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.ORCID 0000-0001-8943-9754
Ori ScottProgram in Genetics and Genome Biology, the Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Samar Z RizviProgram in Genetics and Genome Biology, the Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.ORCID 0009-0009-0546-094X
Wing Suen ChanProgram in Genetics and Genome Biology, the Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.ORCID 0000-0003-3129-6089
Shagana VisuvanathanProgram in Genetics and Genome Biology, the Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Youssif Ben ZablahDepartment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Hongbin LiProgram in Neuroscience and Mental Health, the Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Ameet S SengarProgram in Neuroscience and Mental Health, the Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Michael W SalterDepartment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Zhengping JiaDepartment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Janet RossantDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.ORCID 0000-0002-3731-5466
Ronald D CohnProgram in Genetics and Genome Biology, the Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Bin GuDepartment of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, East Lansing, MI 48824, USA.ORCID 0000-0002-5594-2463
Evgueni A IvakineProgram in Genetics and Genome Biology, the Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.ORCID 0000-0003-2132-4699

Funding

Canadian Child Health Clinician Scientist ProgramCIHR FDN-143334Hospital for Sick ChildrenOntario Ministry of Health and Long-Term CareReverse Rett Research Fund
6 · The paper itself

Abstract

MECP2 duplication syndrome (MDS) is a neurodevelopmental disorder caused by tandem duplication of the MECP2 locus and its surrounding genes, including IRAK1. Current MDS mouse models involve transgenic expression of MECP2 only, limiting their applicability to the study of the disease. Herein, we show that an efficient and precise CRISPR/Cas9 fusion proximity-based approach can be utilized to generate an Irak1-Mecp2 tandem duplication mouse model ('Mecp2 Dup'). The Mecp2 Dup mouse model recapitulates the genomic landscape of human MDS by harboring a 160 kb tandem duplication encompassing Mecp2 and Irak1, representing the minimal disease-causing duplication, and the neighboring genes Opn1mw and Tex28. The Mecp2 Dup model exhibits neuro-behavioral abnormalities, and an abnormal immune response to infection not previously observed in other mouse models, possibly owing to Irak1 overexpression. The Mecp2 Dup model thus provides a tool to investigate MDS disease mechanisms and develop potential therapies applicable to patients.

Indexed as

Disease Models, AnimalGene DuplicationInterleukin-1 Receptor-Associated KinasesMethyl-CpG-Binding Protein 2X-Linked Intellectual DisabilityAnimalsBehavior, AnimalCRISPR-Cas SystemsHumansMaleMiceMice, Inbred C57BLInterleukin-1 Receptor-Associated KinasesIrak1 protein, mouseMecp2 protein, mouseMethyl-CpG-Binding Protein 2Disease modelingIntellectual disabilityInterferonIRAK1MECP2 duplication syndromeMouse model

Identifiers

PMID38881329
PMCPMC11552499

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.