Reduced Mid1 Expression and Delayed Neuromotor Development in daDREAM Transgenic Mice

daDREAM 转基因小鼠中 Mid1 表达降低和神经运动发育延迟

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作者:Mara Dierssen, Laura Fedrizzi, Rosa Gomez-Villafuertes, María Martinez de Lagran, Alfonso Gutierrez-Adan, Ignasi Sahún, Belen Pintado, Juan C Oliveros, Xose M Dopazo, Paz Gonzalez, Marisa Brini, Britt Mellström, Ernesto Carafoli, Jose R Naranjo

Abstract

Downstream regulatory element antagonist modulator (DREAM) is a Ca(2+)-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.

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