THE ONCOGENIC CYSTEINE-RICH LIM DOMAIN PROTEIN RBTN2 IS ESSENTIAL FORERYTHROID DEVELOPMENT

The LIM domain protein rbtn2 is associated with T cell acute leukemias . We demonstrate that rbtn2 is a nuclear protein expressed in the eryt hroid lineage in vivo, and using homologous recombination, we show tha t it is essential for erythroid development in mice. The homozygous rb tn2 null mutation leads to failure of yolk sac erythropoiesis and embr yonic lethality around E10.5. Moreover, in vitro differentiation of yo lk sac tissue from homozygous mutant mice and sequentially targeted do uble-mutant ES cells demonstrates a block to erythroid development. Th is shows a pivotal role for a LIM domain protein in lineage specificat ion during mammalian development and suggests that RBTN2 and GATA-1 ar e critical at similar stages of erythroid differentiation.