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Myeloid differentiation is impaired in transgenic mice with targeted expression of a dominant negative form of retinoid X receptor β
Author(s) -
SUNAGA SHINJI,
MAKI KAZUSHIGE,
LAGASSE ERIC,
BLANCO JORGE C. G.,
OZATO KEIKO,
MIYAZAKI JUNICHI,
IKUTA KOICHI
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.8692483.x
Subject(s) - myelopoiesis , myeloid , transgene , retinoid x receptor , biology , retinoid , endocrinology , genetically modified mouse , medicine , retinoic acid , haematopoiesis , retinoid x receptor alpha , receptor , cancer research , microbiology and biotechnology , stem cell , nuclear receptor , transcription factor , biochemistry , cell culture , genetics , gene
To investigate the in vivo function of retinoid X receptor (RXR) on myelopoiesis, we generated transgenic (Tg) mice with targeted expression of a dominant negative form of RXR β in myeloid cells. In these Tg mice the transgene is expected to suppress the function of heterodimeric receptors composed of RXR and its counterparts, such as retinoic acid receptor. Out of 12 mice analysed, one Tg mouse exhibited a severe maturation arrest at the promyelocytic stage. Three other Tg mice showed a mild inhibition of myeloid differentiation, which was further augmented when mice were treated with 5‐fluorouracil (5‐FU). Furthermore, four Tg mice showed impaired myeloid differentiation in response to the treatment by 5‐FU or granulocyte‐colony stimulating factor (G‐CSF), although they exhibited apparently normal myelopoiesis in the untreated state. The phenotype of Tg mice observed after G‐CSF treatment correlated with the expression level of the transgene, although the correlation was not found in untreated mice. These results indicated that myeloid differentiation is perturbed in the Tg mice by the dominant negative effect of the transgenic RXR, indicating that RXR plays a role in myelopoiesis.