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dc.contributor.authorBarlow, Jillian Len
dc.contributor.authorDrynan, Lesley Fen
dc.contributor.authorHewett, Duncan Ren
dc.contributor.authorHolmes, Luke Ren
dc.contributor.authorLorenzo-Abalde, Silviaen
dc.contributor.authorLane, Alison Len
dc.contributor.authorJolin, Helen Een
dc.contributor.authorPannell, Richarden
dc.contributor.authorMiddleton, Angela Jen
dc.contributor.authorWong, See Hengen
dc.contributor.authorWarren, Alanen
dc.contributor.authorWainscoat, James Sen
dc.contributor.authorBoultwood, Jacquelineen
dc.contributor.authorMcKenzie, Andrewen
dc.date.accessioned2020-01-29T14:33:32Z
dc.date.available2020-01-29T14:33:32Z
dc.date.issued2010-01en
dc.identifier.issn1078-8956
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/301412
dc.description.abstractThe identification of the genes associated with chromosomal translocation breakpoints has fundamentally changed understanding of the molecular basis of hematological malignancies. By contrast, the study of chromosomal deletions has been hampered by the large number of genes deleted and the complexity of their analysis. We report the generation of a mouse model for human 5q- syndrome using large-scale chromosomal engineering. Haploinsufficiency of the Cd74-Nid67 interval (containing Rps14, encoding the ribosomal protein S14) caused macrocytic anemia, prominent erythroid dysplasia and monolobulated megakaryocytes in the bone marrow. These effects were associated with defective bone marrow progenitor development, the appearance of bone marrow cells expressing high amounts of the tumor suppressor p53 and increased bone marrow cell apoptosis. Notably, intercrossing with p53-deficient mice completely rescued the progenitor cell defect, restoring common myeloid progenitor and megakaryocytic-erythroid progenitor, granulocyte-monocyte progenitor and hematopoietic stem cell bone marrow populations. This mouse model suggests that a p53-dependent mechanism underlies the pathophysiology of the 5q- syndrome.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectHematopoietic Stem Cellsen
dc.subjectChromosomes, Mammalianen
dc.subjectAnimalsen
dc.subjectHumansen
dc.subjectMiceen
dc.subjectAnemia, Macrocyticen
dc.subjectMyelodysplastic Syndromesen
dc.subjectDisease Models, Animalen
dc.subjectChromosome Deletionen
dc.subjectApoptosisen
dc.subjectSyntenyen
dc.subjectGenes, p53en
dc.titleA p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome.en
dc.typeArticle
prism.endingPage66
prism.issueIdentifier1en
prism.publicationDate2010en
prism.publicationNameNature medicineen
prism.startingPage59
prism.volume16en
dc.identifier.doi10.17863/CAM.48489
dcterms.dateAccepted2009-10-16en
rioxxterms.versionofrecord10.1038/nm.2063en
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2010-01en
dc.contributor.orcidHolmes, Luke R [0000-0002-6389-5425]
dc.contributor.orcidWarren, Alan [0000-0001-9277-4553]
dc.contributor.orcidBoultwood, Jacqueline [0000-0002-4330-2928]
dc.identifier.eissn1546-170X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/L003368/1)


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