アマノ　ケンジ   Amano   天野　賢治    所属   東邦大学  医学部 医学科（大森病院）    職種   胚培養士
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome.
掲載誌名	正式名：Human molecular genetics ISSNコード：0964-6906
掲載区分	国外
巻・号・頁	13(13),pp.1333-40
著者・共著者	Kenji Amano,Haruhiko Sago,Chiharu Uchikawa,Taishi Suzuki,Svetlana E Kotliarova,Nobuyuki Nukina,Charles J Epstein,Kazuhiro Yamakawa
発行年月	2004/07/01
概要	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 approximately 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.
PMID	15138197