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

Transcriptomic networks implicate neuronal energetic abnormalities in three mouse models harboring autism and schizophrenia-associated mutations

Aaron Gordon, Annika Grønborg-Forsingdal, Ib Vestergaard Klewe, Jacob Nielsen, Michael Didriksen, Thomas Werge, Daniel Geschwind
doi: https://doi.org/10.1101/625368
Aaron Gordon
1Department of Neurology, University of California Los Angeles, Los Angeles, CA
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Annika Grønborg-Forsingdal
2Division of Synaptic Transmission, H. Lundbeck A/S, Valby, Denmark
3Institute of Biological Psychiatry, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ib Vestergaard Klewe
2Division of Synaptic Transmission, H. Lundbeck A/S, Valby, Denmark
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacob Nielsen
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Didriksen
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Werge
4Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark
5Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
6Lundbeck Foundation GeoGenetics Centre, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel Geschwind
7Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, CA
8Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, CA
9Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA
MD PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: dhg@mednet.ucla.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Genetic risk for psychiatric illness is complex, so identification of shared molecular pathways where distinct forms of genetic risk might coincide is of substantial interest. A growing body of genetic and genomic studies suggest that such shared molecular pathways exist across disorders with different clinical presentations, such as schizophrenia and autism spectrum disorder (ASD). But how this relates to specific genetic risk factors is unknown. Further, whether some of the molecular changes identified in brain relate to potentially confounding antemortem or post-mortem factors is difficult to prove. We analyzed the transcriptome from the cortex and hippocampus of three mouse lines modeling human copy number variants (CNVs) associated with schizophrenia and ASD: Df(h15q13)/+, Df(h22q11)/+, and Df(h1q21)/+ which carry the 15q13.3 deletion, 22q11.2 deletion, and 1q21.1 deletion, respectively. Although we found very little overlap of differential expression at the level of individual genes, gene network analysis identified two modules of co-expressed genes that were dysregulated across all three mouse models. One module observed in both cortex and hippocampus was associated with neuronal energetics and firing rate, and overlapped with changes identified in post mortem human brain from SCZ and ASD patients. These data highlight aspects of convergent gene expression in mouse models harboring major risk alleles, and strengthen the connection between neuronal energetic dysfunction and neuropsychiatric disorders in humans.

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 May 02, 2019.
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.
Transcriptomic networks implicate neuronal energetic abnormalities in three mouse models harboring autism and schizophrenia-associated mutations
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Transcriptomic networks implicate neuronal energetic abnormalities in three mouse models harboring autism and schizophrenia-associated mutations
Aaron Gordon, Annika Grønborg-Forsingdal, Ib Vestergaard Klewe, Jacob Nielsen, Michael Didriksen, Thomas Werge, Daniel Geschwind
bioRxiv 625368; doi: https://doi.org/10.1101/625368
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Transcriptomic networks implicate neuronal energetic abnormalities in three mouse models harboring autism and schizophrenia-associated mutations
Aaron Gordon, Annika Grønborg-Forsingdal, Ib Vestergaard Klewe, Jacob Nielsen, Michael Didriksen, Thomas Werge, Daniel Geschwind
bioRxiv 625368; doi: https://doi.org/10.1101/625368

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

  • Bioinformatics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4655)
  • Biochemistry (10309)
  • Bioengineering (7629)
  • Bioinformatics (26208)
  • Biophysics (13454)
  • Cancer Biology (10631)
  • Cell Biology (15354)
  • Clinical Trials (138)
  • Developmental Biology (8458)
  • Ecology (12761)
  • Epidemiology (2067)
  • Evolutionary Biology (16777)
  • Genetics (11365)
  • Genomics (15411)
  • Immunology (10557)
  • Microbiology (25063)
  • Molecular Biology (10163)
  • Neuroscience (54132)
  • Paleontology (398)
  • Pathology (1656)
  • Pharmacology and Toxicology (2878)
  • Physiology (4318)
  • Plant Biology (9206)
  • Scientific Communication and Education (1582)
  • Synthetic Biology (2543)
  • Systems Biology (6757)
  • Zoology (1453)