Regulation of erythropoiesis by the neuronal transmembrane protein Lrfn2.
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.


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.
Castellanos
Andres
A
Institute of Cancer Research, CR-UK Centre for Cell and Molecular Biology, London, UK.
Lang
Georgina
G
Frampton
Jonathan
J
Weston
Kathleen
K
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003114:Colony-Forming Units Assay; D004900:Erythroblasts / Q000166:cytology; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
C524126:Lrfn2 protein, mouse; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger