A “humanized mouse” is a mouse carrying functioning human genes, cells, tissues, and/or organs. Humanized mice are commonly used as small animal models in biological and medical research for human therapeutics. Immunodeficient mice are often used as recipients for human cells or tissues, because they can relatively easily accept heterologous cells due to lack of host immunity. Traditionally, the nude mouse and severe combined immunodeficiency (SCID) mouse have been used for this purpose, but recently the NOG mouse and the NSG mouse have been shown to engraft human cells and tissues more efficiently than other models. Two mouse strains, called MITRG and MISTRG, were described in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. Such humanized mouse models may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.
There are many promising biomedical research applications for human therapeutics including:
- Infectious Diseases
- Hepatitis Virus and liver disease - AFC8/Rag2/gamma c DKO mice
- Regenerative Medicine
- M. Ito and et al. (2002), "NOD/SCID/γnull mouse: an excellent recipient mouse model for engraftment of human cells", Blood 100 (9): 3175–3182, doi:10.1182/blood-2001-12-0207, PMID 12384415
- Shultz LD, Lyons BL, Burzenski LM et al. (2005), "Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells", J. Immunol. 174 (10): 6477–89, PMID 15879151.
- T. Nomura, N. Tamaoki, A. Takakura and et al. (2008), T. Nomura, T. Watanabe, and S. Habu, ed., Basic Concept of Development and Practical Application of Animal Models for Human Diseases, In: Humanized Mice; Current Topics in Microbiology and Immunology, Springer-Verlag, Berlin and Heidelberg, pp. 1–22
- M. Ito, K. Kobayashi12 and T. Nakahata (2008), T. Nomura, T. Watanabe, and S. Habu, ed., NOD/Shi-scid IL2rγnull (NOG) Mice More Appropriate for Humanized Mouse Models; Current Topics in Microbiology and Immunology, Springer-Verlag, Berlin and Heidelberg, pp. 53–76
- McDermott SP, Eppert K, Lechman ER, Doedens M and Dick JE (July 2010), "Comparison of human cord blood engraftment between immunocompromised mouse strains", Blood 116 (2): 193–200, doi:10.1182/blood-2010-02-271841, PMID 20404133.
- Anthony Rongvaux, Tim Willinger, Jan Martinek, Till Strowig, Sofia V Gearty, Lino L Teichmann, Yasuyuki Saito, Florentina Marches, Stephanie Halene, A Karolina Palucka, Markus G Manz & Richard A Flavell (March 2014), "Development and function of human innate immune cells in a humanized mouse model", Nature Biotechnology, doi:10.1038/nbt.2858.
- Brehm, M. A., Wiles, M. V., Greiner, D. L., & Shultz, L. D. (2014). Generation of improved humanized mouse models for human infectious diseases. Journal of immunological methods. http://dx.doi.org/10.1016/j.jim.2014.02.011
- Ito, R., Takahashi, T., Katano, I., & Ito, M. (2012). Current advances in humanized mouse models. Cellular & molecular immunology, 9(3), 208-214. doi:10.1038/cmi.2012.2
- Scheer, N., Snaith, M., Wolf, C. R., & Seibler, J. (2013). Generation and utility of genetically humanized mouse models. Drug discovery today, 18(23), 1200-1211. http://dx.doi.org/10.1016/j.drudis.2013.07.007
- Peltz G. (2013). Can 'humanized' mice improve drug development in the 21st century? Trends Pharmacol Sci.; 34(5), 255-60. doi:10.1016/j.tips.2013.03.005 PMID:23602782
- Grompe, M., & Strom, S. (2013). Mice with human livers. Gastroenterology, 145(6), 1209-1214. http://dx.doi.org/10.1053/j.gastro.2013.09.009
- Leung, C., Chijioke, O., Gujer, C., Chatterjee, B., Antsiferova, O., Landtwing, V., McHugh, D., Raykova, A. and Münz, C. (2013), Infectious diseases in humanized mice. Eur. J. Immunol., 43: 2246–2254. doi:10.1002/eji.201343815