| First Author | Castellanos A | Year | 2007 |
| Journal | Exp Hematol | Volume | 35 |
| Issue | 5 | Pages | 724-34 |
| PubMed ID | 17577922 | Mgi Jnum | J:125805 |
| Mgi Id | MGI:3759944 | Doi | 10.1016/j.exphem.2007.02.004 |
| Citation | Castellanos A, et al. (2007) Regulation of erythropoiesis by the neuronal transmembrane protein Lrfn2. Exp Hematol 35(5):724-34 |
| abstractText | 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. |
