Brain protein changes in Mecp2 mouse mutant models: Effects on disease progression of Mecp2 brain specific gene reactivation.

Brain protein changes in Mecp2 mouse mutant models: Effects on disease progression of Mecp2 brain specific gene reactivation. J Proteomics. 2019 Oct 16;:103537 Authors: Cortelazzo A, De Felice C, Guy J, Timperio AM, Zolla L, Guerranti R, Leoncini S, Signorini C, Durand T, Hayek J Abstract Rett syndrome (RTT) is a leading cause of severe intellectual disability in females, caused by de novo loss-of function mutations in the X-linked methyl-CpG binding protein 2 (MECP2). To better investigate RTT disease progression/pathogenesis animal models of Mecp2 deficiency have been developed. Here, Mecp2 mouse models are employed to investigate the role of protein patterns in RTT. A proteome analysis was carried out in brain tissue from i) Mecp2 deficient mice at the pre-symptomatic and symptomatic stages and, ii) mice in which the disease phenotype was reversed by Mecp2 reactivation. Several proteins were shown to be differentially expressed in the pre-symptomatic (n = 18) and symptomatic (n = 20) mice. Mecp2 brain reactivated mice showed wild-type comparable levels of expression for twelve proteins, mainly related to proteostasis (n = 4) and energy metabolic pathways (n = 4). The remaining ones were found to be involved in redox homeostasis (n = 2), nitric oxide regulation (n = 1), neurodevelopment (n = 1). Ten out of twelve proteins were newly linked to Mecp2 deficiency. Our study sheds light on the relevance of th...
Source: Journal of Proteomics - Category: Biochemistry Authors: Tags: J Proteomics Source Type: research