PT  - JOURNAL ARTICLE
AU  - Phan, BaDoi N.
AU  - Page, Stephanie Cerceo
AU  - Campbell, Morganne N.
AU  - Bohlen, Joseph F.
AU  - Thaxton, Courtney L.
AU  - Simon, Jeremy M.
AU  - Burke, Emily E.
AU  - Shin, Joo Heon
AU  - Kennedy, Andrew J.
AU  - Sweatt, J. David
AU  - Philpot, Benjamin D.
AU  - Jaffe, Andrew E.
AU  - Maher, Brady J.
TI  - Defects of myelination are common pathophysiology in syndromic and idiopathic autism spectrum disorder
AID  - 10.1101/128124
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 128124
4099  - http://biorxiv.org/content/early/2017/05/11/128124.short
4100  - http://biorxiv.org/content/early/2017/05/11/128124.full
AB  - Autism Spectrum Disorder (ASD) is genetically heterogeneous in nature with convergent symptomatology, suggesting dysregulation of common molecular pathways. We analyzed transcriptional changes in the brains of five independent mouse models of Pitt-Hopkins Syndrome (PTHS), a syndromic ASD caused by autosomal dominant mutation in TCF4, and identified considerable overlap in differentially expressed genes (DEGs). Gene and cell-type enrichment analyses of these DEGs identified oligodendrocyte dysregulation that was subsequently validated by decreased protein levels. We further showed significant enrichment of myelination genes was prevalent in two additional mouse models of ASD (Ptenm3m4/m3m4, Mecp2KO). Moreover, we integrated syndromic ASD mouse model DEGs with ASD risk-gene sets (SFARI) and human idiopathic ASD postmortem brain RNA-seq and found significant enrichment of overlapping DEGs and common biological pathways associated with myelination and oligodendrocyte differentiation. These results from seven independent mouse models are validated in human brain, implicating disruptions in myelination is a common ASD pathophysiology.