Hematopoietic progenitor cell abnormalities in Hoxc-8 null mutant mice.

The mammalian Hox genes encode a family of conserved transcription factors that control the establishment of the body plan during embryogenesis. Many Hox genes are also known to be expressed in hematopoietic cells. We found that Hoxc-8, a member of the Hox C cluster, is expressed in the mouse hematopoietic organs, fetal liver and adult bone marrow. To determine the role of Hoxc-8 gene in hematopoiesis, we compared progenitor cell numbers in the fetal liver and adult bone marrow cells. We observed a significant reduction in the number of erythroid burst-forming unit (BFU-E) and in granulocyte/macrophage colony-forming unit (CFU-GM) in the Hoxc-8 null mice, although the peripheral blood cell counts were normal. The hematopoietic cells from the homozygote animals exhibited normal expansion capability in a liquid culture system, suggesting that the decreased number of progenitor cells may be due to a defect extrinsic to the hematopoietic cells, such as in the interaction with the microenvironment.