Regulation of erythropoiesis by the neuronal transmembrane protein Lrfn2.
Exp Hematol
; 35(5): 724-34, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17577922
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 ANDMETHODS:
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. MEnTCD2.5Myc 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
Eritropoese
/
Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article