Evidence map›Paper›PMID 39915488›Full record

ArticleNature communications2025

Endothelial SHANK3 regulates tight junctions in the neonatal mouse blood-brain barrier through β-Catenin signaling.

Yong-Eun Kim, Minseong Kim, Sunwhi Kim, Raham Lee, Yusuke Ujihara, Esther Magdalena Marquez-Wilkins, Yong-Hui Jiang, Esther Yang, Hyun Kim, Changhoon Lee and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–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

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  8. Inflammation increases the penetrance of behavioral impairment inbioRxiv : the preprint server for biology · 2025
    Article
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  10. Review
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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

12 authors.

Yong-Eun KimDepartment of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USA.ORCID http://orcid.org/0009-0002-8036-2492
Minseong Kim *Department of Molecular and Cellular Physiology, Louisiana State University Health Science Center, Shreveport, LA, USA.
Sunwhi Kim *Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USA.ORCID http://orcid.org/0000-0001-5009-5544
Raham Lee *Department of Molecular and Cellular Physiology, Louisiana State University Health Science Center, Shreveport, LA, USA.ORCID http://orcid.org/0000-0002-4928-9517
Yusuke UjiharaDepartment of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USA.ORCID http://orcid.org/0009-0000-6939-9871
Esther Magdalena Marquez-WilkinsNeuroscience Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
Yong-Hui JiangDepartment of Genetics, Pediatrics and Neuroscience, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-6188-8806
Esther YangDepartment of Anatomy, College of Medicine, Korea University, Seoul, South Korea.
Hyun KimDepartment of Anatomy, College of Medicine, Korea University, Seoul, South Korea.ORCID http://orcid.org/0000-0002-7210-5798
Changhoon LeeDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-4031-3795
Changwon ParkDepartment of Molecular and Cellular Physiology, Louisiana State University Health Science Center, Shreveport, LA, USA. changwon.park@lsuhs.edu.ORCID http://orcid.org/0000-0003-0635-921X
Il Hwan KimDepartment of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USA. ikim9@uthsc.edu.ORCID http://orcid.org/0000-0002-8429-1030

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Mechanisms of ER71/ETV2-regulated VascularizationR01HL119291 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PARK, CHANGWON · 2013 to 2022
$3.2M
Losing specificity: the role of the locus coeruleus in age-related distractibilityR01AG075000 · NIA · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI KATZ, BENJAMIN D, KIM, IL HWAN · 2022 to 2024
$2.3M
Genes, Neural Circuits, and BehaviorR01MH117429 · NIMH · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI KIM, IL HWAN · 2019 to 2022
$1.5M
Losing specificity: the role of the locus coeruleus in age-related distractibilityRF1AG075000 · NIA · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI KATZ, BENJAMIN D, KIM, IL HWAN · 2025 to 2025
$1.4M
Genes, Neural Circuits, and BehaviorR56MH117429 · NIMH · DUKE UNIVERSITY · PI KIM, IL HWAN · 2018 to 2018
$400k
NCATS NIH HHS UL1 TR001863NHLBI NIH HHS R01 HL119291NIA NIH HHS R01 AG075000NIA NIH HHS RF1 AG075000NIMH NIH HHS R01 MH117429NIMH NIH HHS R56 MH117429U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MH117429U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG075000
6 · The paper itself

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disability condition arising from a combination of genetic and environmental factors. Despite the blood-brain barrier (BBB) serving as a crucial gatekeeper, conveying environmental influences into the brain parenchyma, the contributions of BBB in ASD pathogenesis remain largely uncharted. Here we report that SHANK3, an ASD-risk gene, expresses in the BBB-forming brain endothelial cells (BECs) and regulates tight junctional (TJ) integrity essential for BBB's barrier function. Endothelium-specific Shank3 (eShank3) knockout (KO) neonatal mice exhibit male-specific BBB-hyperpermeability, reduced neuronal excitability, and impaired ultra-sonic communications. Although BBB permeability is restored during adult age, the male mutant mice display reduced neuronal excitability and impaired sociability. Further analysis reveals that the BBB-hyperpermeability is attributed to the β-Catenin imbalance triggered by eShank3-KO. These findings highlight a pathogenic mechanism stemming from the ASD-risk Shank3, emphasizing the significance of neonatal BECs in the BBB as a potential therapeutic target for ASD.

Indexed as

beta CateninBlood-Brain BarrierEndothelial CellsNerve Tissue ProteinsTight JunctionsAnimalsAnimals, NewbornAutism Spectrum DisorderBrainFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutMicrofilament Proteinsbeta CateninMicrofilament ProteinsNerve Tissue ProteinsShank3 protein, mouse

Identifiers

PMID39915488
PMCPMC11802743

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.