Construction of human-SCID chimeric mice.

Until recently, testing of new therapeutic agents has relied extensively upon the use of mice and nonhuman primates for in vivo preclinical studies. Unfortunately, these animal models do not always mimic the physiological and pathophysiological processes that occur in humans. The finding that C.B-17 severe combined immunodeficiency (SCID) mice lack a competent immune system, and therefore are unable to mount effective cellular and humoral responses to foreign antigens, has led to their use as recipients for xenografts of human tissues. This unit is focused on the construction of human-SCID chimeric through the surgical implantation of human fetal hematolymphoid tissues into SCID mice (SCID-hu mice). The Basic Protocol describes the surgical implantation of human fetal thymus and liver under the kidney capsules of SCID mice (SCID-hu Thy/Liv model). Subcutaneous transplantation of human fetal bone marrow and thymus (SCID-hu Bm/Thy mice) is described in the Alternate Protocol. Additional support protocols provide procedures to analyze human lymphocyte populations in the peripheral blood and grafted organs of SCID-hu mice. The advantages and disadvantages of each protocol and potential applications are discussed in the Commentary.