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Human Molecular Genetics Advance Access originally published online on May 11, 2004
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Human Molecular Genetics, 2004, Vol. 13, No. 13 1333-1340
DOI: 10.1093/hmg/ddh154
Human Molecular Genetics, Vol. 13, No. 13 © Oxford University Press 2004; all rights reserved

Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome

Kenji Amano1, Haruhiko Sago3, Chiharu Uchikawa1, Taishi Suzuki2, Svetlana E. Kotliarova2, Nobuyuki Nukina2, Charles J. Epstein4 and Kazuhiro Yamakawa1,*

1Laboratory for Neurogenetics and 2Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan, 3Division of Fetal Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan and 4Department of Pediatrics, University of California, San Francisco, CA 94143, USA

Received February 23, 2004; Accepted April 28, 2004

Down syndrome (DS) is the most common chromosomally caused form of mental retardation and is caused by trisomy of chromosome 21. The over-expression of genes located on the trisomic region has been assumed to be responsible for the phenotypic abnormalities of DS, but this hypothesis has not been confirmed fully and the very existence of gene dosage effects has been called into question. We have therefore investigated global gene expression profiles in Ts1Cje, a mouse model for DS that displays learning deficits and has a segmental trisomy of chromosome 16 orthologous to a segment of human chromosome 21 spanning from Sod1 to Znf295. DNA microarray analyses of six Ts1Cje and six normal littermate (2N) mouse brains at postnatal day 0 with probe sets representing approximately 11 300 genes revealed that the number of expressed genes and their identities in Ts1Cje mice were almost same in 2N mice. Notably, the expression levels of most genes in the trisomic region were increased ~1.5-fold, and the top 24 most consistently over-expressed genes in the Ts1Cje mice were all located in the trisomic region. In contrast, the expression levels of genes on other chromosomes or the euploid region of chromosome 16 were largely the same (1.0-fold) in Ts1Cje and 2N mice. These results indicate that the genes in the trisomic region of Ts1Cje are over-expressed in a dosage-dependent manner and are implicated in the molecular pathogenesis of DS.

* To whom correspondence should be addressed. Tel: +81 484679703; Fax: +81 484677095; Email: yamakawa{at}brain.riken.jp


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