title: Hematopoietic defects in the Ts1Cje mouse model of Down syndrome.
abstract: Down syndrome (DS) persons are born with various hematopoietic abnormalities, ranging from relatively benign, such as neutrophilia and macrocytosis, to a more severe transient myeloproliferative disorder (TMD). In most cases, these abnormalities resolve in the first few months to years of life. However, sometimes the TMD represents a premalignant disease that develops into acute megakaryocytic leukemia (AMKL), usually in association with acquired GATA1 mutations. To gain insight into the mechanisms responsible for these abnormalities, we analyzed the hematopoietic development of the Ts1Cje mouse model of DS. Our analyses identified defects in mature blood cells, including macrocytosis and anemia, as well as abnormalities in fetal liver and bone marrow stem and progenitor cell function. Despite these defects, the Ts1Cje mice do not develop disease resembling either TMD or AMKL, and this was not altered by a loss of function allele of Gata1. Thus, loss of Gata1 and partial trisomy of chromosome 21 orthologs, when combined, do not appear to be sufficient to induce TMD or AMKL-like phenotypes in mice.
authors.affiliation: Molecular Medicine, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. carmichael@wehi.edu.au
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Carmichael
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Majewski
authors.forename: Warren S
authors.initials: WS
authors.lastname: Alexander
authors.forename: Donald
authors.initials: D
authors.lastname: Metcalf
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Hilton
authors.forename: Chelsee A
authors.initials: CA
authors.lastname: Hewitt
authors.forename: Hamish S
authors.initials: HS
authors.lastname: Scott
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D002891:Chromosomes, Human, Pair 21; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D050982:GATA1 Transcription Factor / Q000235:genetics; D006402:Hematologic Diseases / Q000209:etiology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000473:pathology; D016019:Survival Analysis; D013922:Thrombocytosis / Q000473:pathology
chemical_list: D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse