RT Journal Article
SR Electronic
T1 Defects of myelination are common pathophysiology in syndromic and idiopathic autism spectrum disorders
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 128124
DO 10.1101/128124
A1 BaDoi N. Phan
A1 Stephanie Cerceo Page
A1 Morganne N. Campbell
A1 Joseph F. Bohlen
A1 Courtney L. Thaxton
A1 Jeremy M. Simon
A1 Emily E. Burke
A1 Joo Heon Shin
A1 Andrew J. Kennedy
A1 David Sweatt
A1 Benjamin D. Philpot
A1 Andrew E. Jaffe
A1 Brady J. Maher
YR 2017
UL http://biorxiv.org/content/early/2017/04/18/128124.abstract
AB 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.