Proteomic analysis of cortical brain tissue from the BTBR mouse model of autism: Evidence for changes in STOP and myelin-related proteins

Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. However, the widely accepted biomarkers for autism are still lacking. In this study, we carried out a quantitative proteomic profiling study of cortical brain tissue from BTBR T(+)Itpr3(tf) (BTBR) mice, a mouse model that displays an autism-like phenotype. Using isobaric tag for relative and absolute quantification (iTRAQ) coupled with LC-MS/MS, a total of 3611 proteins were quantitated in mouse cortices. As compared to C57BL/6J (B6) mice, 126 differentially expressed proteins were found in the brain from BTBR mice. The functional annotation and categories of differentially expressed proteins were analyzed. Especially, the stable tubule only polypeptide (STOP) protein and myelin-related proteins down-regulated significantly in BTBR mice were confirmed by Western blotting. Furthermore, the BTBR mice displayed reduced levels of staining with ferric alum in comparison to B6 controls, indicative of myelin disruption. Finally, we propose that reduced STOP expression in the brain could be involved in the mediation of autism-like behaviors through impairments of myelination in oligodendrocytes and synaptic function in neurons. Manipulation of STOP protein could be a promising avenue for therapeutic interventions to autism.