RNA-Seq of Men1-KO mouse hippocampus

Rett syndrome is a neurodevelopmental disorder and is associated with a variety of genetic mutations, such as FoxG1. However, the panel of genetic risk factors for Rett syndrome have not been fully elucidated. Here we report that both deficiency and overexpression of neuronal Menin result in Rett syndrome-like behaviors, including social defects, increased repetitive behaviors and cognition impairments. Multifaceted transcriptome analyses revealed that FoxG1 expression is altered in Men1 deficiency mice, through its regulation over Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) signaling. Such changes were rescued by expression of full-length FoxG1, accompanied by normalized spine growth and hippocampal synaptic plasticity. Taken together, these results indicate a putative role of Menin in maintaining FoxG1 expression, and Menin signaling may serve as Rett syndrome therapeutic targets.