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dc.contributor.authorCastellanos, Aen_US
dc.contributor.authorLang, Gen_US
dc.contributor.authorFrampton, Jen_US
dc.contributor.authorWeston, Ken_US
dc.identifier.citationEXPERIMENTAL HEMATOLOGY, 2007, 35 pp. 724 - 734en_US
dc.description.abstractObjective. The transgenic mouse line MEnTCD2.5 expresses a dominant interfering Myb protein in a T-cell-specific fashion. When MEnTCD2.5 animals are crossed to a second line ubiquitously expressing Myc, they develop a rapid onset, fatal disease characterized by enlarged lymph nodes full of nonlymphoid cells. This study aimed to elucidate the reason for this anomalous non-T-cell phenotype. Materials and Methods. We studied the cells by morphological analysis, surface marker staining, mRNA expression studies and in vitro colony-forming assays. Results. Aberrant cells in MEnTCD2.5 lymph nodes are erythroblasts, and cooperation between MEnTCD2.5 and Myc causes severe erythroblastosis, but not erythroleukemia. MEnTCD2.5:Myc and MEnTCD2.5 animals have pronounced extramedullary erythropoiesis in their lymph nodes, and some increase in bone marrow-derived erythroid progenitors; no other MEnTCD2 transgenic line cooperates in this fashion with Myc, suggesting that the MEnTCD2.5 integration site, in intron 2 of the Lrfn2 gene, is of importance. To confirm this, in in vitro colony-forming assays, expression of wild-type Lrfn2 phenocopies the MEnTCD2.5 defect. Finally, Lrfn2 expression also causes the outgrowth of a bizarre cell type in colony-forming assays that stains positively for both early hematopoietic and fibroblast/fibrocyte surface markers. Conclusions. The Lrfn2 protein, a transmembrane adhesion-type molecule, is able to subvert hematopoietic differentiation to increase erythropoiesis. In cooperation with Myc, this leads to erythroblastosis. Lrfn2 may also be involved in colony forming units-fibroblast regulation. As Lrfn2 expression is detectable in wild-type bone marrow, it likely plays a novel role during normal hematopoiesis. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc.en_US
dc.format.extent724 - 734en_US
dc.titleRegulation of erythropoiesis by the neuronal transmembrane protein Lrfn2en_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
pubs.notesaffiliation: Weston, K (Reprint Author), Inst Canc Res, London SW3 6JB, England. Inst Canc Res, London SW3 6JB, England. Univ Birmingham, Sch Med, Inst Biomed Res, Birmingham B15 2TT, W Midlands, England. keywords-plus: ADHESION-LIKE MOLECULES; TRANSCRIPTION FACTOR; IN-VITRO; HEMATOPOIETIC DEVELOPMENT; STRESS ERYTHROPOIESIS; CELL-DIFFERENTIATION; GENE-EXPRESSION; MOUSE EMBRYOS; MICE LACKING; C-KIT research-areas: Hematology; Research & Experimental Medicine web-of-science-categories: Hematology; Medicine, Research & Experimental author-email: researcherid-numbers: Castellanos, Andres/F-3302-2016 funding-acknowledgement: Medical Research Council [G9818340B] number-of-cited-references: 43 times-cited: 6 usage-count-last-180-days: 0 usage-count-since-2013: 2 journal-iso: Exp. Hematol. doc-delivery-number: 164GB unique-id: ISI:000246220500004 da: 2018-08-31en_US
pubs.notesNot knownen_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorWeston, Kathleenen_US

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