title: An extra human chromosome 21 reduces mlc-2a expression in chimeric mice and Down syndrome.
abstract: An extra copy of human chromosome 21 (Chr 21) causes Down syndrome (DS), which is characterized by mental retardation and congenital heart disease (CHD). Chimeric mice containing Chr 21 also exhibit phenotypic traits of DS including CHD. In this study, to identify genes contributing to DS phenotypes, we compared the overall protein expression patterns in hearts of Chr 21 chimeras and wild type mice by two-dimensional electrophoresis. The endogenous mouse atrial specific isoform of myosin light chain-2 (mlc-2a) protein was remarkably downregulated in the hearts of chimeric mice. We also confirmed that the human MLC-2A protein level was significantly lower in a human DS neonate heart, as compared to that of a normal control. Since mouse mlc-2a is involved in heart morphogenesis, our data suggest that the downregulation of this gene plays a crucial role in the CHD observed in DS. The dosage imbalance of Chr 21 has a trans-acting effect which lowers the expression of other genes encoded elsewhere in the genome.
authors.affiliation: Department of Human Genome Science, Life Sciences Division, Graduate School of Medicine, Tottori University, Nishimachi 86, Yonago, Tottori 683-8503, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishigaki
authors.forename: Tokuyuki
authors.initials: T
authors.lastname: Shinohara
authors.forename: Tosifusa
authors.initials: T
authors.lastname: Toda
authors.forename: Akira
authors.initials: A
authors.lastname: Omori
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Ichinose
authors.forename: Masayuki
authors.initials: M
authors.lastname: Itoh
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shirayoshi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kurimasa
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Oshimura
mesh_terms: D000818:Animals; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002678:Chimera; D002891:Chromosomes, Human, Pair 21; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D018628:Gene Dosage; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D018994:Myosin Light Chains; D012333:RNA, Messenger; C107184:myosin light chain 2; D024722:Cardiac Myosins