Impaired erythropoiesis in transgenic mice overexpressing a truncated erythropoietin receptor.
Erythropoietin (EPO), one of the pivotal regulators of erythrocyte production, transmits signals through the EPO receptor (EPOR). We have previously reported that human bone marrow (BM) cells express two dominant forms of the EPOR, one full-length and one truncated (EPOR-F and EPOR-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 show the presence in mouse BM of a truncated form of the EPOR that is essentially 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 was induced experimentally in these mice, however, both lines showed apparently poor recovery resulting in higher mortality than wild-type control mice. The impaired erythropoiesis found in these mice thus strongly suggests the EPOR-T's role as a negative regulator of erythropoiesis in vivo.
Nakamura
Y
Y
Institute of Basic Medical Sciences and Center for TARA, University of Tsukuba, Tsukuba City, Japan.
Takano
H
H
Osawa
M
M
Tomita
T
T
Kim
D K
DK
Kojima
M
M
Motohashi
T
T
Miyoshi
S
S
Hiroyama
T
T
Tokumoto
Y
Y
Nakauchi
H
H
D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002452:Cell Count; D003114:Colony-Forming Units Assay; D004920:Erythropoiesis / Q000502:physiology*; D005260:Female; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010659:Phenylhydrazines; D010976:Platelet Count; D012313:RNA / Q000032:analysis; D017467:Receptors, Erythropoietin / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D010659:Phenylhydrazines; D017467:Receptors, Erythropoietin; C030299:phenylhydrazine; D012313:RNA