Humanized mouse models for study human diseases and biomedical research

Animal models are used as surrogates of human biology due to the ethical restrictions of working with cell and tissue samples from human donors. Humanized mice are permitting significant progress in studies of human infectious disease, cancer, regenerative medicine, graft versus host disease, allergies, and immunity. simple definition of humanized mice, mice engrafted with functional human cells or tissues or expressing human transgenes and as preclinical models for the in vivo study of human cells and tissues have been development for over 30 years.Three main breakthroughs occurred in this field;First, the Prkdcscid, mutation in CB17 mice (scid). Limitations human cell engraftments in SCID include the spontaneous generation of mouse T- and B-cells during aging and high levels of host NK-cell and other innate immune activity. Thesecond, non-obese diabetic (NOD)-scid mice. the use of NOD-scid limited by their short life, and activity of NK cells and other components of innate immunity.thethird, targeted mutations at the IL-2R γ-chain locus (Il2rg). These mice support greatly increased engraftment of human tissue, HSCs and MCS compared with all previously immunodeficient humanized mouse models. Absence of the IL2rg leads to severe impairments in T- and B-cell function, and completely prevents NK-cell development. Crossing the IL2rgnull mutation to mice homozygous for the Prkdcscid (severe combined immunodeficiency [SCID]), recombination activating gene 1 (Rag1null) or recombination activating gene 2 (Rag2null) mutations allowed for heightened human engraftment of both lymphoid and myeloid cells and supported the development of a more complete human immune system following transplantation with cell and tissue. There are three major immunodeficient mouse stocks that are widely currently used: NSG (NOD.Cg- Prkdc SCID Il2rg tm1Wjl /Sz), NOG (NODShi.Cg-Prkdc scid Il2rg tm1Sug) and BRG (C; 129S4- Rag2 tm1.1Flv Il2rg tm1.1Flv) mice. This review discusses recent progress in the development and use of humanized mice, and highlights their utility for the study of human diseases.

کلیدواژه ها:

Humanized mouse models ، IL-2R γ-chain locus ، Transplantation ، NSG ، NOG ، BRG