Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: challenging the gene dosage effect hypothesis (Part II) |
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| Authors: | Cheon M S Bajo M Kim S H Claudio J O Stewart A K Patterson D Kruger W D Kondoh H Lubec G |
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| Institution: | (1) Department of Pediatrics, University of Vienna, Vienna, Austria, AT;(2) Institute of Neuroimmunology, SAS, Bratislava, Slovakia, SK;(3) Experimental Therapeutics, Toronto General Research Institute, Toronto, Canada, CA;(4) Eleanor Roosevelt Institute, Denver, Colorado, U.S.A., US;(5) Department of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania, U.S.A., US;(6) Department of Developmental Biology, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan, JP |
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| Abstract: | Summary. Down syndrome (DS) is the most common genetic cause of mental retardation. To explain the impact of extra chromosome 21 in
the pathology of DS, gene dosage effect hypothesis has been proposed, but several investigators including our group have challenged
this hypothesis. Although analysis of the sequence of chromosome 21 has been essentially completed, the molecular and biochemical
mechanisms underlying the pathology are still unknown. We therefore investigated expression levels of six proteins encoded
on chromosome 21 (HACS1, DYRK1A, αA-crystallin, FTCD, GARS-AIRS-GART, and CBS) in fetal cerebral cortex from DS and controls at 18–19 weeks of gestational age
using Western blot analysis. Protein expression of HACS1 was significantly and remarkably decreased in DS, and the expression
levels of five proteins were comparable between DS and controls suggesting that the gene dosage effect hypothesis is not sufficient
to fully explain the DS phenotype. We are continuing to quantify proteins whose genes are encoded on chromosome 21 in order
to provide a better understanding of the pathobiochemistry of DS at the protein level.
Received July 1, 2002 Accepted July 19, 2002 Published online November 14, 2002
Acknowledgement This work was supported, in part (Dr. D. Patterson), by the National Institute of Child Health and Human Development (NICHD;
HD17449).
Authors' address: Prof. Dr. Gert Lubec, CChem, FRSC (UK), Department of Pediatrics, University of Vienna, Waehringer Guertel 18, A-1090 Vienna,
Austria, Fax: +43-1-40400-3194, E-mail: gert.lubec@akh-wien.ac.at
Abbreviations: DS, Down syndrome; HACS1, hematopoietic adapter containing Src homology 3 domain and sterile α motifs; DYRK1A, dual specificity tyrosine phosphorylated and regulated kinase; αA-crystallin, alpha crystallin subunit A; FTCD, formi-minotransferase cyclodeaminase; GARS-AIRS-GART, glycinamide ribonucleotide
synthetase-aminoimidazole ribonucleotide synthetase-glycinamide ribonucleotide formyltransferase; CBS, cystathionine β-synthase; NSE, neuron specific enolase; GFAP, glial fibrillary acidic protein |
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| Keywords: | : Chromosome 21 Down syndrome HACS1 DYRK1A alphaA-crystallin FTCD GARS-AIRS-GART CBS |
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