Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Defects of myelination are common pathophysiology in syndromic and idiopathic autism spectrum disorders

View ORCID ProfileBaDoi N. Phan, Stephanie Cerceo Page, Morganne N. Campbell, Joseph F. Bohlen, Courtney L. Thaxton, Jeremy M. Simon, Emily E. Burke, Joo Heon Shin, Andrew J. Kennedy, David Sweatt, Benjamin D. Philpot, Andrew E. Jaffe, Brady J. Maher
doi: https://doi.org/10.1101/128124
BaDoi N. Phan
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for BaDoi N. Phan
Stephanie Cerceo Page
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Morganne N. Campbell
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joseph F. Bohlen
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Courtney L. Thaxton
Neuroscience Center, The University of North Carolina, Chapel Hill, NC,Department of Cell Biology and Physiology, The University of North Carolina, Chapel Hill, NC,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeremy M. Simon
Neuroscience Center, The University of North Carolina, Chapel Hill, NC,Department of Genetics, The University of North Carolina, Chapel Hill, NC,Carolina Institute for Developmental Disabilities, The University of North Carolina, Chapel Hill, NC,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emily E. Burke
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joo Heon Shin
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew J. Kennedy
Department of Chemistry, Bates College, Lewiston, ME,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Sweatt
Department of Pharmacology, Vanderbilt University, Nashville, TN,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benjamin D. Philpot
Neuroscience Center, The University of North Carolina, Chapel Hill, NC,Department of Cell Biology and Physiology, The University of North Carolina, Chapel Hill, NC,Carolina Institute for Developmental Disabilities, The University of North Carolina, Chapel Hill, NC,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew E. Jaffe
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD,Department of Biostatistics Johns Hopkins Bloomberg School of Public Health, Baltimore, MD,Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Andrew.Jaffe@libd.org Brady.Maher@libd.org
Brady J. Maher
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD,Department of Psychiatry and Behavioral Sciences Johns Hopkins School of Medicine, Baltimore, MD,Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Andrew.Jaffe@libd.org Brady.Maher@libd.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Autism spectrum disorder (ASD) affects approximately 1:68 individuals and has incalculable burdens on affected individuals, their families, and health care systems. While the genetic contributions to idiopathic ASD are heterogeneous and largely unknown, the causal mutations for syndromic forms of ASD – including truncations and copy number variants – provide a genetic toehold with which to gain mechanistic insights1-3. Models of these syndromic disorders have been used to better characterize the molecular and physiological processes disrupted by these mutations4. Two fundamental questions remain – how biologically similar are the mouse models of syndromic forms of ASD, and how relevant are these mouse models to their human analogs? To address these questions, we performed integrative transcriptomic analyses of seven independent mouse models of three syndromic forms of ASD generated across five laboratories, and assessed dysregulated genes and their pathways in human postmortem brain from patients with ASD and unaffected controls. These cross-species analyses converged on shared disruptions in myelination and axon development across both syndromic and idiopathic ASD, highlighting both the face validity of mouse models for these disorders and identifying novel convergent molecular phenotypes amendable to rescue with therapeutics.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted April 18, 2017.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Defects of myelination are common pathophysiology in syndromic and idiopathic autism spectrum disorders
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Defects of myelination are common pathophysiology in syndromic and idiopathic autism spectrum disorders
BaDoi N. Phan, Stephanie Cerceo Page, Morganne N. Campbell, Joseph F. Bohlen, Courtney L. Thaxton, Jeremy M. Simon, Emily E. Burke, Joo Heon Shin, Andrew J. Kennedy, David Sweatt, Benjamin D. Philpot, Andrew E. Jaffe, Brady J. Maher
bioRxiv 128124; doi: https://doi.org/10.1101/128124
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Defects of myelination are common pathophysiology in syndromic and idiopathic autism spectrum disorders
BaDoi N. Phan, Stephanie Cerceo Page, Morganne N. Campbell, Joseph F. Bohlen, Courtney L. Thaxton, Jeremy M. Simon, Emily E. Burke, Joo Heon Shin, Andrew J. Kennedy, David Sweatt, Benjamin D. Philpot, Andrew E. Jaffe, Brady J. Maher
bioRxiv 128124; doi: https://doi.org/10.1101/128124

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (1526)
  • Biochemistry (2480)
  • Bioengineering (1738)
  • Bioinformatics (9683)
  • Biophysics (3903)
  • Cancer Biology (2971)
  • Cell Biology (4194)
  • Clinical Trials (135)
  • Developmental Biology (2627)
  • Ecology (4102)
  • Epidemiology (2031)
  • Evolutionary Biology (6898)
  • Genetics (5206)
  • Genomics (6501)
  • Immunology (2184)
  • Microbiology (6945)
  • Molecular Biology (2752)
  • Neuroscience (17281)
  • Paleontology (126)
  • Pathology (427)
  • Pharmacology and Toxicology (706)
  • Physiology (1057)
  • Plant Biology (2489)
  • Scientific Communication and Education (643)
  • Synthetic Biology (831)
  • Systems Biology (2689)
  • Zoology (430)