Persistent Unresolved Inflammation in the Mecp2-308 Female Mutated Mouse Model of Rett Syndrome.

Alessio Cortelazzo,Roberto Guerranti,Monica Pescaglini,Claudio De Felice,Joussef Hayek,Anna Maria Timperio,Silvia Leoncini,Lucia Ciccoli,Bianca De Filippis,Lello Zolla,Laura Ricceri,Giovanni Laviola,Cinzia Signorini

doi:10.1155/2017/9467819

Abstract

Rett syndrome (RTT) is a rare neurodevelopmental disorder usually caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2). Several Mecp2 mutant mouse lines have been developed recapitulating part of the clinical features. In particular, Mecp2-308 female heterozygous mice, bearing a truncating mutation, are a validated model of the disease. While recent data suggest a role for inflammation in RTT, little information on the inflammatory status in murine models of the disease is available. Here, we investigated the inflammatory status by proteomic 2-DE/MALDI-ToF/ToF analyses in symptomatic Mecp2-308 female mice. Ten differentially expressed proteins were evidenced in the Mecp2-308 mutated plasma proteome. In particular, 5 positive acute-phase response (APR) proteins increased (i.e., kininogen-1, alpha-fetoprotein, mannose-binding protein C, alpha-1-antitrypsin, and alpha-2-macroglobulin), and 3 negative APR reactants were decreased (i.e., serotransferrin, albumin, and apolipoprotein A1). CD5 antigen-like and vitamin D-binding protein, two proteins strictly related to inflammation, were also changed. These results indicate for the first time a persistent unresolved inflammation of unknown origin in the Mecp2-308 mouse model.

Highlights

Rett syndrome (RTT, MIM 312750) is a progressive neurodevelopmental disorder, affecting almost exclusively the female gender
Rett syndrome (RTT) is a rare neurodevelopmental disorder usually caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2)
These results indicate for the first time a persistent unresolved inflammation of unknown origin in the Mecp2-308 mouse model

Summary

Introduction

Rett syndrome (RTT, MIM 312750) is a progressive neurodevelopmental disorder, affecting almost exclusively the female gender. With a frequency of approximately 1 : 10,000 live births, it is a leading cause of severe intellectual disability and autistic features in females [1, 2]. The classical clinical picture of the disease [3] is characterized by a period of 6 to 18 months of apparently normal neurodevelopment followed by an early neurological regression, with a progressive loss of acquired cognitive, social, and motor skills in a typical. It has become apparent that there is a spectrum of severity in RTT, as some patients may present with atypical features, sometimes overlapping with autism spectrum disorders [3,4,5]. RTT is known to be caused in the overwhelming majority of cases by sporadic de novo loss-of-function mutations in the X-linked methyl-CpGbinding protein 2 (MECP2) gene [6] encoding methyl-

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