title: Comparative proteomic profiling reveals aberrant cell proliferation in the brain of embryonic Ts1Cje, a mouse model of Down syndrome.
abstract: To identify molecular candidates involved in brain disabilities of Ts1Cje, a mouse model of Down syndrome (DS), we performed comparative proteomic analyses. Proteins extracted from the brains of postnatal wild-type (WT) and Ts1Cje mice were analyzed by two-dimensional gel electrophoresis (2-DE). No differences were detected in the proteins expressed in the whole brain between WT and Ts1Cje mice at postnatal day 0 and 3months of age. Five spots with differential expression in the brains of Ts1Cje mice were detected by 2-DE of brain proteins from WT and Ts1Cje embryos at embryonic day 14.5 (E14.5). These differentially expressed proteins in Ts1Cje embryos were identified as calcyclin-binding protein (CACYBP), nucleoside diphosphate kinase-B (NDPK-B), transketolase (TK), pyruvate kinase (PK), and 60S acidic ribosomal protein P0 (RPLP0) by peptide mass fingerprinting. CACYBP and NDPK-B were involved in cell proliferation, whereas TK and PK were associated with energy metabolism. Experiments on cell proliferation, an in vivo bromodeoxyuridine (BrdU)-labeling experiment, and immunohistochemical analysis for phospho-histone H3 (an M-phase marker) demonstrated increased numbers of BrdU-positive and M-phase cells in the ganglionic eminence. Our findings suggest that the dysregulated expression of proteins demonstrated by comparative proteomic analysis could be a factor in increased cell proliferation, which may be associated with abnormalities in DS brain during embryonic life.
authors.affiliation: Department of Pathological Biochemistry, Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan; Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan. Electronic address: ishihara@mb.kyoto-phu.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Ishihara
authors.affiliation: Department of Pathological Biochemistry, Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kanai
authors.affiliation: Center for Maternal-Fetal and Neonatal Medicine, National Center for Child Health and Development, 2-10-1 Okura Setagaya-ku, Tokyo 157-8535, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sago
authors.affiliation: Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamakawa
authors.affiliation: Department of Pathological Biochemistry, Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Akiba
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000378:metabolism*; D004622:Embryo, Mammalian; D051379:Mice; D008810:Mice, Inbred C57BL; D040901:Proteomics / Q000379:methods*
keywords: Down syndrome; brain development; cell proliferation; comparative proteomics