In these www.selleckchem.com/products/FTY720.html models, transplantation of human hematopoietic CD34+ cells into immunodeficient mice leads to the development of all human lymphoid lineages and the repopulation of lymphoid organs with human cells. These models differ according to the mouse strains used (i.e., NOD/SCID, NOG/SCID, or RAG2?/?��c?/? mice) and the origins of the human hematopoietic cells transplanted (i.e., CD34+ cells from fetal liver or cord blood). Previously, we showed sustained and disseminated HIV replication in RAG2?/?��c?/? mice transplanted with cord blood CD34+ cells after intraperitoneal (i.p.) injection of HIV (3). So far, only two studies investigating HIV infection in humanized mice have shown successful HIV infection by the rectal route (4, 37). In these studies, human transplants were obtained from fetal tissue.

Aside from any ethical considerations, fetal tissue is not as easily and widely available as cord blood. Furthermore, one study used bone marrow/liver/thymus (BLT) mice, which receive a thymic organ transplant before irradiation and reconstitution with fetal liver-derived hematopoietic stem cells. In the present study, we examined mucosal transmission of HIV in RAG2?/?��c?/? mice transplanted with cord blood-derived CD34+ cells. We characterized the engraftment of human cells into the gastrointestinal tract of these humanized mice and determined their susceptibility to rectal transmission of HIV. We challenged mice with cell-free and cell-associated HIV since their relative contributions are not known.

Overall, rectal transmission rates were low in all groups of humanized mice, independently of preinfection treatment and inoculation protocols. (This work was presented in part as a poster at the HIV Pathogenesis Keystone Symposia, Banff, Alberta, Canada, 27 March to 1 April 2008.) MATERIALS AND METHODS Generation of humanized mice. Mice were reconstituted as described previously (3, 39). Briefly, newborn RAG2?/?��c?/? mice were irradiated with 2 �� 2 Gy. CD34+ cells were isolated from cord blood with immunomagnetic beads (Milteny Biotec), and 150,000 to 400,000 cells (246,000 �� 60,000) were transplanted into each mouse. Fetal liver-derived CD34+ cells were a kind gift from R. Akkina (Colorado State University). Eight to 12 weeks after transplantation, the levels of blood engraftment were determined by flow cytometry of peripheral blood mononuclear Dacomitinib cells (PBMCs) stained for the human panleukocyte marker CD45 in all mice (mean human cells/live cells, 11.56% �� 10.9%). Liver, bone marrow, and spleen engraftment levels were also analyzed in 14 mice. All experiments were approved and conducted according to local guidelines and laws. Tissue characterization.