Authors: R FerrandoMiguel M S Cheon G Lubec
Publish Date: 2004/03/16
Volume: 26, Issue: 3, Pages: 255-261
Abstract
Down Syndrome DS trisomy 21 is the most common genetic cause of mental retardation The completed sequencing of genes encoded on chromosome 21 provides excellent basic information however the molecular mechanisms leading to the phenotype of DS remain to be elucidated Although overexpression of chromosome 21 encoded genes has been documented information at the protein expression level is mandatory as it is the proteins that carry out function We therefore decided to evaluated expression level of seven proteins whose genes are encoded on chromosome 21 DSCR4 DSCR5 DSCR6 KIR42 GIRK2 KCNE1 and KCNE2 in fetal cortex brain of DS and controls at the early second trimester of pregnancy by Western blotting βactin and neuron specific enolase NSE were used to normalise cell loss and neuronal loss DSCR5 PIGP a component of glycosylphosphatidylinositolNacetylglucosaminyltransferase GPIGnT was overexpressed about twofold even when levels were normalised with NSE DSCR6 was overexpressed in addition but when normalised versus NSE levels were comparable to controls DSCR4 was not detectable in fetal brain Potassium channels KIR42 and GIRK2 were comparable between DS and controls whereas KCNE1 and KCNE2 were not detectable Quantification of these proteins encoded on chromosome 21 revealed that not all gene products of the DS critical region are overexpressed in DS brain early in life indicating that the DS phenotype cannot be simply explained by the gene dosage effect hypothesis Overexpression of PIGP DSCR5 may lead to or represent impaired glycosylphosphatidylinositolNacetylglucosaminyltransferase mediated posttranslational modifications and subsequent anchoring of proteins to the plasma membrane
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