Immunodeficient mouse model for human hematopoietic stem cell engraftment and immune system development.

Immunodeficient mice engrafted with human immune systems provide an exciting model to study human immunobiology in an in vivo setting without placing patients at risk. The essential parameter for creation of these "humanized models" is engraftment of human hematopoietic stem cells (HSC) that will allow for optimal development of human immune systems. However, there are a number of strategies to generate humanized mice and specific protocols can vary significantly among different laboratories. Here we describe a protocol for the co-implantation of human HSC with autologous fetal liver and thymic tissues into immunodeficient mice to create a humanized model with optimal human T cell development. This model, often referred to as the Thy/Liv or BLT (bone marrow, liver, thymus) mouse, develops a functional human immune system, including HLA-restricted human T cells, B cells, and innate immune cells.