Dysregulated ERK signal pathway and immune profiles in Fragile X Syndrome

Fragile X Syndrome (FXS) is the leading cause of inherited mental retardation, and the most common identified genetic cause of autism. Lack of production of the Fragile X Mental Retardation Protein (FMRP) leads to changes in dendritic morphology and resultant cognitive and behavioral manifestations characteristic of individuals with FXS. FMRP is an RNA-binding protein that is believed to regulate the translation of a large number of other proteins, leading to a complex and variable set of symptoms in FXS. In a mouse model of FXS, we previously observed delayed initiation of synaptically localized protein synthesis in response to neurotransmitter stimulation, as compared to wild-type mice. We now likewise have observed delayed early-phase phosphorylation of extracellular-signal regulated kinase (ERK), a nodal point for cell signaling cascades, in both neurons and thymocytes of fmr-1 KO mice. We further reported that early-phase kinetics of ERK activation in lymphocytes from human peripheral blood is delayed in a cohort of individuals with FXS, relative to normal controls, suggesting a potential biomarker to measure metabolic status of disease for individuals with FXS. Furthermore, dysregulated phosphatases, especially Protein phosphatase 2A (PP2A) may account for the delay in ERK activation. FXS and immune dysregulation is an emerging area in FXS research. We hypothesize that immune cells from FXS patients may have different gene expression and protein profiles. We first analyzed genome-wide microarray data from FXS lymphoblastoid cell, and found several immune gene sets are differentially expressed in FXS patients. We further reported that the cytokine profiles and cytokines activation profiles are dysregulated in FXS patients. These results could be used as potential cellular markers for FXS patients.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Cell and Developmental Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2012

Author dc:creator

• Weng, Ning

Contributors dc:contributor

• Cox, Charles L.
• Kemper, Byron W.
• Ceman, Stephanie S.
• Newmark, Phillip A.
• Pilas, Barbara

• Fragile X Syndrome
• extracellular-signal regulated kinase
• extracellular-signal regulated kinase (ERK)
• Mitogen-activated protein kinases (MAPK)
• biomarker
• cytokine profiles
• flow cytometry

Statement dc:rights

• Copyright 2012 Ning Weng

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/32022

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/32022