Vitamin A deficiency in mice causes a systemic expansion of myeloid cells

To examine the role of retinoids in hematopoietic cell growth in vivo, we s tudied female SENCAR mice made vitamin A deficient by dietary restriction. Deficient mice exhibited a dramatic increase in myeloid cells in bone marro w, spleen, and peripheral blood. The abnormal expansion of myeloid cells wa s detected from an early stage of vitamin A deficiency and contrasted with essentially normal profiles of T and B lymphocytes. This abnormality was re versed on addition of retinoic acid to the vitamin A-deficient diet, indica ting that the myeloid cell expansion is a direct result of retinoic acid de ficiency. TUNEL analysis indicated that spontaneous apoptosis, a normal pro cess in the life cycle of myeloid cells, was impaired in vitamin A-deficien t mice, which may play a role in the increased myeloid cell population. Qua ntitative reverse transcriptase-polymerase chain reaction analysis of purif ied granulocytes showed that expression of not only RAR, but RXRs, 2 nuclea r receptors that mediate biologic activities of retinoids, was significantl y reduced in cells of deficient mice, This work shows that retinoids critic ally control the homeostasis of myeloid cell population in vivo and suggest s that deficiency in this signaling pathway may contribute to various myelo proliferative disorders, (Blood, 2000;95: 3349-3356) (C) 2000 by The Americ an Society of Hematology.