Myeloid differentiation is impaired in transgenic mice with targeted expression of a dominant negative form of retinoid X receptor beta.
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 beta in myeloid cells. In these Tg mice the transgene is expected to suppress the function of hetero dimeric 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 on 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.
Sunaga
S
S
Department of Disease-related Gene Regulation Research (Sandoz), Faculty of Medicine, University of Tokyo, Japan.
Maki
K
K
Lagasse
E
E
Blanco
J C
JC
Ozato
K
K
Miyazaki
J
J
Ikuta
K
K
D000818:Animals; D015139:Blotting, Southern; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D018168:Receptors, Retinoic Acid / Q000378:metabolism*
D018168:Receptors, Retinoic Acid; D016179:Granulocyte Colony-Stimulating Factor