Excessive Cap-dependent Translation as a Molecular Mechanism of ASD

The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. 14. ABSTRACT We hypothesize that excessive cap-dependent translation is a causative factor in autism spectrum disorder (ASD). To test this hypothesis, we have been studying transgenic mice that overexpress eIF4E have been testing the following specific aims: 1) to determine whether eIF4E transgenic mice display behaviors consistent with ASD, 2) to determine whether ASD-like behaviors displayed by eIF4E transgenic mice can be reversed by novel cap-dependent translation inhibitors, and 3) to determine whether eIF4E transgenic mice display cellular and molecular abnormalities due to excessive cap-dependent translation. mice. Our studies will provide information concerning whether overexpression of eIF4E is a biological risk factor for ASD. Our studies also will provide important information concerning the role of upregulated cap-dependent translation in ASD, and could link ASD mechanistically at the level of cap-dependent translational control to fragile X syndrome (FXS), tuberous sclerosis complex (TSC), and autistic patients with PTEN and EIF4E mutations. Moreover, the results of these studies would provide information for the design and use of compounds to therapeutically target eIF4E-eIF4G interactions and eIF4A for treating patients with ASD.