NOVEL B219 OB RECEPTOR ISOFORMS - POSSIBLE ROLE OF LEPTIN IN HEMATOPOIESIS AND REPRODUCTION/

Hematopoietic development is a complex process that involves a large n umber of growth factors and cytokines. Many cytokines are known to act on more mature, lineage-restricted cells of the hematopoietic system( 1,2). However, no specific factors have yet been identified that induc e the expansion of the most primitive hematopoietic cells without also inducing differentiation. To search for such factors, we isolated nov el cell lines from the yolk sac in order to identify genes important i n early hematopoietic and endothelial development. This approach led t o the discovery of B219, a sequence that is expressed in at least four isoforms in very primitive hematopoietic cell populations and which m ay represent a novel hemopoietin receptor. The recently published rece ptor(3) for the obesity (ob) gene product (leptin)(4) is an isoform of B219 with a nearly identical ligand binding domain. B279/obr is expre ssed in the yolk sac, early fetal liver, enriched hematopoietic stem c ells and in a variety of lymphohematopoietic cell lines. B279/obr is a lso expressed at high levels in adult reproductive organs. B279/obr ma ps to human chromosome 1p32, a region syntenic with the recently repor ted location of obr on murine chromosome 4 (ref. 5).