Reduced Mid1 expression and delayed neuromotor development in daDREAM transgenic mice

Abstract

Downstream regulatory element antagonist modulator (DREAM) is a C a2+-binding protein that binds DNA and represses transcription in a Ca 2+-dependent manner. Previous work has shown a role for DREAM in cerebellar function regulating the expression of the sodium/calcium exchanger 3 (NCX3) in cerebellar granular neurons to control Ca 2+ homeostasis and survival of these neurons. To achieve a global view of the genes regulated by DREAM in the cerebellum, we performed a genome-wide analysis in transgenic cerebellum expressing a Ca 2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Here we show that DREAM regulates the expression of the midline 1 (Mid1) gene early after birth. As a consequence, daDREAM mice exhibit a significant shortening of the rostro-caudal axis of the cerebellum and a delay in neuromotor development early after birth. Our results indicate a role for DREAM in cerebellar function. © 2012 Dierssen, Fedrizzi, Gomez-Villafuertes, de Lagran, Gutierrez-Adan, Sahún, Pintado, Oliveros, Dopazo, Gonzalez, Brini, Mellström, Carafoli and Naranjo.