Overexpression of Interferon α/β Receptor β Chain in Fetal Down Syndrome Brain

Abstract

Background: Down syndrome (DS; trisomy 21) is the most common chromosomal aberration, with an incidence of 1/700 live births, and presents with mental retardation, typical phenotype and a series of associated pathological conditions. Although overexpression of genes encoded on chromosome 21 was proposed to lead to the phenotype, this has not been fully addressed at the protein level. Aim: It was therefore the aim of our study to determine protein levels of several chromosome 21 gene products in fetal DS brain. We selected interferon (IFN) α/β receptor β chain (IFNAR2), glutamate receptor 5 (ionotropic kainate 1), h2 calponin, claudin-8 and oligodendrocyte transcription factor 1 for quantification in fetal brain of the early second trimester using immunoblotting. Results: We observed significant and about twofold overexpression of the 20-kD immunoreactive IFN receptor α/β band in the fetal cortex of DS brain (p = 0.0293), while the 70-kD immunoreactive band was overexpressed but did not reach statistical significance (p = 0.065). When data were normalized to the housekeeping protein β-actin, a significant increase in IFN receptor levels was observed. Levels of the aforementioned proteins were comparable between DS and controls. Conclusion: Overexpression of IFNAR2 in fetal DS brain may increase the responsiveness of DS cells, leading to altered neuronal excitability, neuronal growth and survival as well as cytoskeleton derangement.