beta-Amyloid precursor protein, ETS-2 and collagen alpha 1 (VI) chain precursor, encoded on chromosome 21, are not overexpressed in fetal Down syndrome: further evidence against gene dosage effect

Down syndrome (DS) is the most common human chromosomal abnormality caused by an extra copy of chromosome 21 and characterized clinically by somatic a nomalies, mental retardation and precocious dementia. The phenotype of DS i s thought to result from overexpression of a gene or genes located on the t riplicated chromosome or chromosome region. Reports that challenge this not ion, however, have been published. To add to this body of evidence, the exp ression of beta -amyloid precursor protein (APP), ETS-2 and collagen alpha1 (VI) chain precursor, encoded on chromosome 21, was investigated in fetal brain by western blot and two-dimensional electrophoresis (2-DE). Western b lot detected APP and ETS-2 that migrated at similar to 75 and 50kDa, respec tively. Subsequent densitometric analysis of APP and ETS-2 immunoreactivity did not produce any significant change between controls and DS. Since the metabolic fate of APP determines the propensity of amyloid beta production, the expression of the secreted forms of APP (sAPP) had been examined. Neit her the expression of sAPP alpha nor sAPP beta showed any detectable change s among the two groups. Collagen alpha1 (VI) chain precursor, a protein res olved as a single spot on 2D gel was identified by matrix associated laser desorption ionization mass spectroscopy. Quantitative analysis of this spot using the 2D Image Master software revealed a significant decrease in feta l DS (P < 0.01) compared to controls. Linear regression analysis did not sh ow any correlation between protein levels and age. The current data suggest that overexpression per se can not fully explain the DS phenotype.