Moreover, in analyses targeting the bone marrow and peripheral blood, differences in susceptibilities to benzene tended to be greater in lymphoid cells than in myeloid cells. These results suggested that interspecies differences in benzene-induced hematotoxicity are mainly due to differences in toxic VE-822 responses in lymphoid cells, in the regulation of benzene in lymphoid development, or both. We speculate that there may be interspecies differences in the regulation of MEF2c expression by benzene on the basis of the reasons stated above. In conclusion, a human-like hematopoietic lineage established in NOG mice by transplanting human hematopoietic stem/ progenitor cells exhibited human-like susceptibility to at least 1 hematotoxicant, benzene. Hu-NOG and Mo-NOG mice offer a well-defined, reproducible, and easy-to-manipulate in vivo system for performing species-specific biochemical analyses of benzene metabolism. We think it is reasonable to assume that Hu-NOG mice will provide a powerful in vivo tool for assessing the hematotoxicity of chemical and physical agents on human hematopoietic cells. In the future, the similarities of the hematotoxic responses induced in Hu-NOG mice and humans should be evaluated more carefully by analyzing the detailed toxic response mechanism in Hu-NOG mice. Our strategy may be applicable to the study of other organs and other toxicants as well. G protein-coupled receptors constitute the largest superfamily of cell surface receptors and regulate the cellular responses to a broad spectrum of extracellular signals, such as hormones, neurotransmitters, chemokines, proteinases, odorants, light and calcium ions. All GPCRs share a common molecular topology with a hydrophobic core of seven membranespanning a-helices, three intracellular loops, three extracellular loops, an N-terminus outside the cell, and a C-terminus inside the cell. The proper function of GPCRs is largely determined by the highly regulated intracellular trafficking of the receptors. GPCRs are synthesized in the ER and after proper folding and correct assembly, they transport to the cell surface en route through the Golgi apparatus and trans-Golgi network. As the first step in post-translational biogenesis, the efficiency of ER export of nascent GPCRs plays a crucial role in the regulation of maturation, cell-surface expression, and physiological functions of the receptors. Great progress has been made on the understanding of GPCR export from the ER over the past decade. However, the underlying molecular mechanisms remain much less-well understood as compared with extensive studies on the events involved in the endocytic and recycling pathways. It has been demonstrated that, similar to many other plasma membrane proteins, GPCRs must first attain native conformation in order to exit from the ER. It is also clear that GPCR export from the ER is modulated by direct interactions with a multitude of regulatory proteins such as ER chaperones and receptor activity modifying proteins, which may stabilize receptor conformation, facilitate receptor maturation and promote receptor delivery to the plasma membrane. More interestingly, a number of highly conserved, specific sequences or motifs embedded within the receptors have recently been indentified to dictate receptor export from the ER. Although the molecular mechanisms underlying the function of these motifs remain elusive, they may modulate proper receptor folding in the ER or receptor interaction with specific components of transport machinery. There are three a2-AR subtypes, designated as a2A-AR, a2BAR, and a2C-AR. It has been known that both a2A-AR and a2B-AR mainly express at the cell surface, whereas a2C-AR cellsurface expression depends on the cell types.