Fragile X syndrome, which is closely associated with autism, is a single-gene disorder caused by the lack of a protein that suppresses protein synthesis. A fragile X mouse model has been shown to exhibit increased protein synthesis in the brain.

What’s more, a direct link between autism and protein synthesis has been seen in a boy with classic autism with a chromosome translocation that maps to the eIF4E gene. This gene encodes a protein that is intimately involved in regulating protein synthesis. In addition, two unrelated families with a history of autism have been found to harbor the same eIF4E mutation, which increases expression of the protein. An increase in eIF4E protein would be expected to increase protein synthesis.

Eric Klann and his colleagues at New York University have found that increased protein synthesis in the brains of transgenic mice that overexpress eIF4E leads to behavioral abnormalities, including repetitive behaviors, that are consistent with autism. They also showed that communication between neurons in the cortex and the striatum, brain regions involved in repetitive behaviors, is altered in the mice.

Klann’s team aims to determine the specific type of neurons that are involved in the altered cortico-striatal communication in the mice, and to determine whether the morphology of the cortico-striatal neurons is altered.

Finally, they plan to identify the proteins that are improperly regulated in the striatum of eIF4E transgenic mice. These studies may provide important information concerning the role of improperly regulated protein synthesis in autism, and could link autism and fragile X mechanistically at the level of protein synthesis.