IMPAIRED ERYTHROPOIESIS IN TRANSGENIC MICE OVEREXPRESSING A TRUNCATEDERYTHROPOIETIN RECEPTOR

Erythropoietin (EPO), one of the pivotal regulators of erythrocyte pro duction, transmits signals through the EPO receptor (EPOR). We have pr eviously reported that human bone marrow (BM) cells express two domina nt forms of the EPOR, one full-length and one truncated (EPOR-F and EP OR-T). Experiments with a cell line have shown that the EPOR-T acts as a dominant-negative regulator of EPOR-F-mediated signals. Its role in erythropoiesis in vivo, however, has yet to be clarified. Here we sho w the presence in mouse BM of a truncated form of the EPOR that is ess entially the same as EPOR-T in humans. To investigate its role in vivo , we generated transgenic mice overexpressing mouse EPOR-T (EPOR-T-Tg mice). As a result, two independent EPOR-T-Tg lines were established. One line revealed mild anemia, but another line did not. When anemia w as induced experimentally in these mice, however, both lines showed ap parently poor recovery resulting in higher mortality than wild-type co ntrol mice. The impaired erythropoiesis found in these mice thus stron gly suggests the EPOR-T's role as a negative regulator of erythropoies is in vivo.