NOD-scid IL2rγnull Mouse Model of Human Skin Transplantation and Allograft Rejection

Abstract

Background-Transplantation of human skin on immunodeficient mice that support engraftment with functional human immune systems would be an invaluable tool for investigating mechanisms involved in wound healing and transplantation. NOD-scid IL2rγ null (NSG) readily engraft with human immune systems but human skin graft integrity is poor. In contrast, human skin graft integrity is excellent on CB17-scid bg (SCID.bg) mice, but they engraft poorly with human immune systems.

Human allograft rejection in humanized mice: a historical perspective

“…However, human skin grafts on unmanipulated NSG mice showed extensive perivascular infiltration of murine immune cells that resulted in graft injury and precluded the study of rejection mediated by human immune cells. 44 The depletion of Gr1 1 murine innate immune cells from the recipient NSG mice allowed transplanted human skin to heal efficiently and significantly improved the overall graft morphology, as evident by the maintenance of epidermal and dermal structures. Moreover, human 'passenger' leukocytes were readily detectable in human skin grafts on Gr1-depleted NSG, an observation that had not been reported previously.…”

“…40,41 This mouse model has been successfully used to examine both allo-immunity and viral immunity and to recapitulate HIV infection. 40,[42][43][44][45] One complicating factor with the Hu-PBL-SCID model is the development of a xenogeneic graft-versus-host disease (GVHD) that develops with successful engraftment as human T cells recognize murine major histocompatibility complex. 27,41,[46][47][48] This GVHD limits the time frame of experiments that can be done with the HU-PBL-SCID mice, but T cells expanded during the xenogeneic reaction still are able to mediate rejection of human skin allografts.…”

Patient-Derived-Tumor-Xenograft: modeling cancer for basic and translational cancer research

“…NSG mice are Scid deficient (bearing a DNA repair complex protein Prkdc mutation) resulting in profound defects in both B and T cells. They also harbor a target mutation of the gene encoding the IL2-receptor common y chain (IL2rg null ) and the lack of signaling through IL2rg results in the functional impairment of NK cells, thus severely compromising both the innate and adaptive immunities in these animals [15]. Moreover, engineered NSG mice have emerged for specific application (i.e.…”

“…Since then, the availability of unique immune-deficient mice has significantly increased [15]. This has led to improved tumor engraftment rates and a wider usage of PDTX models.…”

Immunological Considerations for Inducing Skin Graft Tolerance

“…Humanized mouse system for the study of skin grafts and wound healing Racki et al (2010) compared usage of NOD-scid IL2rgamma(null) mouse (NSG) vs. the CB17-scid bg (SCID.bg) mouse to study skin allograft survival vs. rejection. They found that components of the human immune successfully engrafted into the NSG mouse, but that skin graft survival was poor.…”