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Regulation of erythropoiesis by the neuronal transmembrane protein Lrfn2

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Date
2007-05
ICR Author
Weston, Kathleen
Author
Castellanos, A
Lang, G
Frampton, J
Weston, K
Type
Journal Article
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Abstract
Objective. 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.
URI
https://repository.icr.ac.uk/handle/internal/2494
DOI
https://doi.org/10.1016/j.exphem.2007.02.004
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Language
eng
License start date
2007-05
Citation
EXPERIMENTAL HEMATOLOGY, 2007, 35 pp. 724 - 734
Publisher
ELSEVIER SCIENCE INC

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