PT  - JOURNAL ARTICLE
AU  - BaDoi N. Phan
AU  - Stephanie Cerceo Page
AU  - Morganne N. Campbell
AU  - Joseph F. Bohlen
AU  - Courtney L. Thaxton
AU  - Jeremy M. Simon
AU  - Emily E. Burke
AU  - Joo Heon Shin
AU  - Andrew J. Kennedy
AU  - David Sweatt
AU  - Benjamin D. Philpot
AU  - Andrew E. Jaffe
AU  - Brady J. Maher
TI  - Defects of myelination are common pathophysiology in syndromic and idiopathic autism spectrum disorders
AID  - 10.1101/128124
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 128124
4099  - http://biorxiv.org/content/early/2017/04/18/128124.short
4100  - http://biorxiv.org/content/early/2017/04/18/128124.full
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.