The saga of the humanized mouse: a giant leap into the galaxy or a small step for humankind?
DOI:
https://doi.org/10.48165/jlas.2019.1.1.3Keywords:
humanized mice, transgenic, immunologyAbstract
Laboratory animals have contributed greatly in understanding human physiology and pathology. However, differences in biology do not allow us to definitively interpret the results of experiments in animals. Transplanting human cells and tissues into mice has therefore been one of the milestones in humanizing laboratory animals. However, this necessitates complete replacement of the mouse system by the human system, the most explored of which is the immune system. But this has not been easy as each phenotypic deletion in mice has unraveled the complexity of host (mouse) defense mechanisms and at the same time shed more light on the development of the human immune system. Because humanized immune mice lack the armory to reject xenotransplants, they are being extensively used to implant and study other human systems, including infectious diseases. This review summarizes the history of humanizing the mouse, the technical advancements, the knowledge gained in the process, their use as well as the outlook in this fascinating and rapidly advancing field.
Downloads
References
Abedi MR, Christensson B, Islan KB, Hammarstrom L, Smith CI (1992). Immunoglobulin production in severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood mononuclear cells. Eur. J. Immunol. 22:823-828.
Aldrovandi GM, Feuer G, Gao L, et al. (1993). The SCID-hu mouse as a model for HIV-1 infection. Nature. 363:732-736.
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003). Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA. 100:3983-3988.
Ando K, Muguruma Y, Yahata T (2008). Humanizing bone marrow in immune-deficient mice. Curr. Topics. Microbiol. Immunol. 324:78-86.
Anfossi N, Andre P, Guia S, et al. (2006). Human NK cell education by inhibitory receptors for MHC class I. Immunity. 25:331-342.
Arai F, Hirao A, Ohmura M et al. (2004). Tie2/ angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. 118:149-161.
Auffray I, Dubart A, Izac B, Vainchenker W, Coulombel L (1994). A murine stromal cell line promotes the proliferation of the human factor-dependent leukemic cell line UT-7. Exp. Hematol. 22:417-424.
Baenziger S, Tussiwand R, Schlaepfer E, et al. (2006). Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2−/−γc−/− mice. Proc. Natl. Acad. Sci. USA. 103:15951-15956.
Baenziger S, Ziegler P, Mazzucchelli L, Bronz L, Speck RF, Manz MG (2008). Human T cell development and HIV infection in human hemato-lymphoid system mice. Curr. Topics. Microbiol. Immunol. 324:125-131.
Becker PD, Legrand N, van Geelen CM, et al. (2010). Generation of human antigen-specific monoclonal IgM antibodies using vaccinated “human immune system” mice. PLoS One. 5:e13137.
Bennett CL, van Rijn E, Jung S, et al. (2005). Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity. J. Cell. Biol. 169:569-576.
Bensidhoum M, Chapel A, Francois S. et al. (2004). Homing of in vitro expanded Stro-1− or Stro-1+ human mesen chymal stem cells into the NOD/SCID mouse and their role in supporting human CD34 cell engraftment. Blood. 103:3313-3319.
Bente DA, Melkus MW, Garcia JV, Rico-Hesse R (2005). Dengue fever in humanized NOD-SCID mice. J. Virol. 79:13797-13799.
Bhatia M, Wang JC, Kapp U, Bonnet D, Dick JE (1997). Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc. Natl. Acad. Sci. USA. 94:5320-5325.
Blunt T, Finnie NJ, Taccioli GE, et al. (1995). Defective DNA-dependent protein kinase activity is linked to VDJ recombination and DNA repair defects associated with the murine scid mutation. Cell. 80:813-823.
Bock TA, Orlic D, Dunbar CE, Broxmeyer HE, Bodine DM (1995). Improved engraftment of human hematopoietic cells in severe combined immunodeficient (SCID) mice carrying human cytokine transgenes. J. Exp. Med. 182:2037-43.
Bosma GC, Custer RP and Bosma MJ (1983). A severe combined immunodeficiency mutation in the mouse. Nature. 301:527-530.
Bosma MJ (1992). B and T cell leakiness in the scid mouse mutant. Immunodeficiency Rev. 3:261-276.
Brenner S, Whiting-Theobald N, Kawai T, et al. (2004). CXCR4-transgene expression significantly improves marrow engraftment of cultured hematopoietic stem cells. Stem Cells. 22:1128-1133.
Bresalier RS, Raper SE, Hujanen ES, Kim YS (1987). A new animal model for human colon cancer metastasis. Int. J. Cancer. 39:625-630.
Calvi LM, Adams GB, Weibrecht KW, et al. (2003). Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 425:841-846.
Camacho RE, Wnek R, Shah K, et al. (2004). Intra-thymic/ splenic engraftment of human T cells in HLADR1 transgenic NOD/scid mice. Cell Immunol. 232:86-95.
Camargo FD, Finegold M, Goodell MA (2004). Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners. J. Clin. Invest. 113, 1266-70.
Cao X, Shores EW, Hu-Li J, et al. (1995). Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. Immunity. 2:223-238.
Carballido JM, Namikawa R, Carballido-Perrig N, Antonenko S, Roncarolo MG, de Vries JE (2000). Generation of primary antigen-specific human T- and B-cell responses in immunocompetent SCID-hu mice. Nat. Med. 6:103-106.
Cha JH, Chang MY, Richardson JA, Eidels L (2003). Transgenic mice expressing the diphtheria toxin receptor are sensitive to the toxin. Mol. Microbiol. 49:235-240.
Chen Q, Khoury M, Chen J (2009). Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice. Proc. Natl. Acad. Sci. USA. 106:21783-21788.
Cheung C, Gonzalez FJ (2008). Humanized mouse lines and their application for prediction of human drug metabolism. J. Pharmacol. Exp. Ther. 327:288-299.
Christianson SW, Greiner DL, Hesselton RA, et al. (1997). Enhanced human CD4+ T cell engraftment in beta2- microglobulin-deficient NOD-scid mice. J. Immunol. 158:3578-3586.
Saga of humanized mouse, Nagendra R. H.
Christianson SW, Greiner DL, Schweitzer IB, et al. (1996). Role of natural killer cells on engraftment of human lymphoid cells and on metastasis of human T-lymphoblastoid leukemia cells in C57BL/6J-scid mice and in C57BL/6J-scid bg mice. Cell Immunol. 171:186-199.
Conget PA, Minguell JJ (1999). Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J. Cell Physiol. 181:67-73.
Cornil I, Man S, Fernandez B, Kerbel RS (1989). Enhanced tumorigenicity, melanogenesis, and metastases of a human malignant melanoma after subdermal implan tation in nude mice. J. Natl. Cancer Inst. 81:938-944.
Custer RP, Bosma GC, Bosma MJ (1985). Severe combined immunodeficiency (SCID) in the mouse. Pathology, reconstitution, neoplasms. Am. J. Pathol. 120:464-477.
Delhem N, Hadida F, Gorochov G, et al. (1998). Primary Th1 cell immunization against HIVgp160 in SCID-hu mice coengrafted with peripheral blood lymphocytes and skin. J. Immunol. 161:2060-2069.
Dewan MZ, Terashima K, Taruishi M, et al. (2003). Rapid tumor formation of human T-cell leukemia virus type 1-infected cell lines in novel NODSCID/gc null mice: suppression by an inhibitor against NF-kappaB. J. Virol.
77:5286-5294.
Dewan MZ, Uchihara JN, Terashima K, et al. (2006). Efficient intervention of growth and infiltration of primary adult T-cell leukemia cells by an HIV protease inhibitor, ritonavir. Blood. 107:716-724.
Dewan MZ, Watanabe M, Ahmed S, et al. (2005). Hodgkin’s lymphoma cells are efficiently engrafted and tumor marker CD30 is expressed with constitutive nuclear
factor-kappaB activity in unconditioned NOD/SCID/gc mice. Cancer Sci. 96:466-473.
Dewan MZ, Watanabe M, Terashima K, et al. (2004). Prompt tumor formation and maintenance of constitutive NF-kappaB activity of multiple myeloma cells in NOD/ SCID/gc null mice. Cancer Sci. 95:564-568.
Di Santo JP, Muller W, Guy-Grand D, Fischer A, Rajewsky K (1995). Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain. Proc. Natl. Acad. Sci. USA. 92:377-381.
Diwan BA, Rice JM, Ohshima M, Ward JM (1986). Interstrain differences in susceptibility to liver carcinogenesis initiated by N-nitrosodiethylamine and its promotion by phenobarbital in C57BL/6NCr, C3H/ HeNCrMTV- and DBA/2NCr mice. Carcinogenesis. 7:215-220.
Duffield JS, Forbes SJ, Constandinou CM, et al. (2005). Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J. Clin. Invest. 115:56-65.
Ishikawa F, Shimazu H, Shultz LD, et al. (2006). Purified human hematopoietic stem cells contribute to the generation of cardiomyocytes through cell fusion. FASEB J. 20:950-952.
Ishikawa F, Yasukawa M, Lyons B, et al. (2005). Development of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chain null mice. Blood. 106:1565-1573.
Ishikawa F, Yoshida S, Saito Y, et al. (2007). Chemotherapy resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat. Biotechnol. 25:1315-1321.
Ito M, Hiramatsu H, Kobayashi K, et al. (2002). NOD/SCID/ γc null mouse: an excellent recipient mouse model for engraftment of human cells. Blood. 100:3175-3182.
Ito M, Kobayashi K, Nakahata T (2008a). NOD/Shi-scid IL2rg null (NOG) mice more appropriate for humanized mouse models. Curr. Topics Microbiol. Immunol. 324:54-76.
Ito R, Shiina M, Saito Y, Tokuda Y, Kametani Y, Habu S (2008b). Antigen-specific antibody production of human B cells in NOG mice reconstituted with the human immune system. Curr. Topics Microbiol. Immunol. 324:95-107.
Jaiswal S, Pearson T, Friberg H, et al. (2009). Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NOD-scid IL2Rγnull mice. PLoS One 4:e7251.
Jung S, Unutmaz D, Wong P, et al. (2002). In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity. 17:211-220.
Kagi D, Ledermann B, Burki K, et al. (1994). Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature. 369:31-37.
Kamimura H, Nakada N, Suzuki K, et al. (2010). Assessment of chimeric mice with humanized liver as a tool for predicting circulating human metabolites. Drug Metab. Pharmacokinet. 25:223-235.
Kamogawa Y, Minasi LA, Carding SR, Bottomly K, Flavell RA (1993). The relationship of IL-4- and IFNγ-producing T cells studied by lineage ablation of IL-4-producing cells. Cell. 75:985-995.
Katoh M, Yokoi T (2007). Application of chimeric mice with humanized liver for predictive ADME. Drug Metab. Rev. 39:145-157.
Kennedy MK, Glaccum M, Brown SN, et al. (2000). Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J. Exp. Med.191:771-780.
Saga of humanized mouse, Nagendra R. H.
Kiel M, Ylimaz OH, Iwashita T, Ylimaz OH, Terhorst D, Morrison SJ (2005). SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 121:1109-1121.
Kipps TJ (1989). The CD5 B cell. Adv. Immunol. 47:117-185.
Kirchgessner CU, Patil CK, Evans JW, et al. (1995). DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science. 267:1178-1183.
Koc ON, Gerson SL, Cooper BW, et al. (2000). Rapid hematopoietic recovery after coinfusion of autologous blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J. Clin. Oncol. 18:307-316.
Koyanagi Y, Takana Y, Ito M, Yamamoto N (2008). Humanized mice for human retrovirus infection. Curr. Topics Microbiol. Immunol. 324:133-148.
Koyanagi Y, Tanaka Y, Kira J, et al. (1997a). Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL immunodeficient mouse strain. J. Virol. 71:2417-2424.
Koyanagi Y, Tanaka Y, Tanaka R, et al. (1997b). High levels of viremia in hu-PBL-NOD-scid with HIV-1 infection. Leukemia. 11 Suppl 3:109-112.
Krause DS, Theise ND, Collector MI, et al. (2001). Multi organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell. 105:369-377.
Kuroiwa Y, Yoshida H, Ohshima T, et al. (2002). The use of chromosome-based vectors for animal transgenesis. Gene Therapy. 9:708-712.
Larochelle A, Vormoor J, Hanenberg H, et al. (1996). Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implications for gene therapy. Nat. Med. 2:1329-1337.
Legrand N, Cupedo T, van Lent AU, et al. (2006). Transient accumulation of human mature thymocytes and regulatory T cells with CD28 superagonist in “human immune system” Rag2−/−γc−/− mice. Blood. 108:238-245.
Li C, Heidt DG, Dalerba P, et al. (2007). Identification of pancreatic cancer stem cells. Cancer Res. 67:1030-1037.
Lin JH (2008). Applications and limitations of genetically modified mouse models in drug discovery and devel opment. Curr. Drug Metab. 9:419-438.
Lowry PA, Shultz LD, Greiner DL, et al. (1996). Improved engraftment of human cord blood stem cells in NOD/ LtSz-scid/scid mice after irradiation or multiple-day injections into unirradiated recipients. Biol. Blood Marrow Transplant. 2:15-23.
Ema H, Sudo K, Seita J, et al. (2005). Quantification of self-renewal capacity in single hematopoietic stem cells from normal and lnk-deficient mice. Dev. Cell. 8:907-914.
Faulkner L, Borysiewicz LK, Man S (1998). The use of human leucocyte antigen class I transgenic mice to investigate human immune function. J. Immunol. Methods. 221:1-16.
Flatz L, Rieger T, Merkler D, et al. (2010). T cell dependence of Lassa fever pathogenesis. PLoS Pathog. 6:e1000836.
Friese MA, Jensen LT, Willcox N, Fugger L (2006). Humanized mouse models for organ-specific
autoimmune diseases. Curr. Opin. Immunol.
18:704-709.
Fu XY, Huang G, Matsumoto M, Molina H, Chaplin DD (1997a). Independent signals regulate development of primary and secondary follicle structure in spleen and mesenteric lymphnode. Proc. Natl. Acad. Sci. USA. 94:5739-5743.
Fu YX, Molina H, Matsumoto M, Huang G, Min J, Chaplin DD (1997b). Lymphotoxin-alpha (LTa) supports devel opment of splenic follicular structure that is required for IgG responses. J. Exp. Med. 185:2111-2120.
Fujino H, Hiramatsu J, Tsuchiya A, et al. (2007). Human cord blood CD34+ cells develop into hepatocytes in the livers of NOD/SCID/gcnull mice through cell fusion. FASEB J. 21:3499-3510.
Galy A, Travis M, Cen D, Chen B (1995). Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. Immunity. 3:459-473.
Giovanella BC, Fogh J (1985). The nude mouse in cancer research. Adv. Cancer Res. 44:69-120.
Gorantla S, Santos K, Meyer V, et al. (2005). Human dendritic cells transduced with herpes simplex virus amplicons encoding human immunodeficiency virus type 1 (HIV-1) gp120 elicit adaptive immune responses from human cells engrafted into NOD/SCID mice and confer partial protection against HIV-1 challenge. J. Virol. 79:2124-2132.
Gorantla S, Sneller H, Walters L, et al. (2007). Human immunodeficiency virus type 1 pathobiology studied in humanized BALB/c-Rag2−/−γc−/− mice. J. Virol. 81:2700-2712.
Greiner DL, Hesselton RA. Shultz LD (1998). SCID mouse models of human stem cell engraftment. Stem Cells. 16:166-177.
Guenechea G, Gan OI, Dorrell C, Dick JE (2001). Distinct classes of human stem cells that differ in proliferative and self-renewal potential. Nat. Immunol. 2:75-82.
Habu S, Fukui H, Shimamura K, et al. (1981). In vivo effects of anti-asialo GM1. I. Reduction of NK activity and enhancement of transplanted tumor growth in nude mice. J. Immunol. 127:34-38.
Harris RG, Herzog EL, Bruscia EM, Grove JE, Van Arnam JS, Krause DS (2004). Lack of fusion requirement for bone marrow-derived epithelia. Science. 305:90-93.
Hess D, Li L, Martin M, et al. (2003). Bone marrow derived stem cells initiate stem cell regeneration. Nat. Biotechnol. 21:763-770.
Heyman RA, Borrelli E, Lesley J, et al. (1989). Thymidine kinase obliteration: creation of transgenic mice with controlled immune deficiency. Proc. Natl. Acad. Sci. USA. 86:2698-2702.
Hiramatsu H, Nishikomori R, Heike T, et al. (2003). Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/gc null mice model. Blood. 102:873-880.
Horie H, Koike S, Kurata T, et al. (1994). Transgenic mice carrying the human poliovirus receptor: new animal models for study of poliovirus neurovirulence. J. Virol. 68:681-688.
Hudson WA, Li Q, Le C, Kersey JH (1998).
Xenotransplantation of human lymphoid malignancies is optimized in mice with multiple immunologic defects. Leukemia. 12:2029-2033.
Huntington ND, Di Santo JP (2008). Humanized immune system (HIS) mice as a tool to study human NK cell development. Curr. Topics Microbiol. Immunol. 324:109-124.
Ianus A, Holz GG, Theise ND, Hussain MA (2003). In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J. Clin. Invest. 111:843-850.
Iliopoulos D, Ernst C, Steplewski Z, et al. (1989). Inhibition of metastases of a human melanoma xenograft by monoclonal antibody to the GD2/GD3 gangliosides. J. Natl. Cancer Inst. 81:440-444.
Imada K, Takaori-Kondo A, Akagi T, et al. (1995). Tumorigenicity of human T-cell leukemia virus type I-infected cell lines in severe combined immunodefi cient mice and characterization of the cells proliferating in vivo. Blood. 86:2350-2357.
Ince WL, Zhang L, Jiang Q, Arrildt K, Su L, Swanstrom R (2010). Evolution of the HIV-1 env gene in the Rag2-/- γC-/- humanized mouse model. J. Virol. 84:2740-2752.
Ishikawa F, Saito Y, Yoshida S, Harada M, Shultz LD (2008). The differentiative and regenerative properties of human hematopoietic stem/ progenitor cells in NOD-SCID/ IL2rγnull mice. Curr. Topics Microbiol. Immunol. 324:87-94. Ma N, Ladilov Y, Kaminski A, et al. (2006). Umbilical cord blood cell transplantation for myocardial regeneration. Transplant Proc. 38:771-773.
Majumdar MK, Thiede MA, Mosca JD, Moorman M, Gerson SL (1998). Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells. J. Cell Physiol. 176:57-66.
Masuda H, Maruyama T, Hiratsu E, et al. (2007). Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/γc null immunodeficient mice. Proc. Natl. Acad. Sci. USA. 104:1925-1930.
Masuda H, Okano HJ, Maruyama T, Yoshimura Y (2008). In vivo imaging in humanized mice. Curr. Topics Microbiol. Immunol. 324:179-196.
Matsumura H, Hasuwa H, Inoue N, Ikawa M, Okabe M (2004). Lineage-specific cell disruption in living mice by Cre-mediated expression of diphtheria toxin A chain. Biochem. Biophys. Res. Commun. 321:275-279.
Matsumura T, Kametani Y, Ando K, et al. (2003). Functional CD5+B cells develop predominantly in the spleen of NOD/SCID/γc null (NOG) mice transplanted either with human umbilical cord blood, bone marrow, or mobilized peripheral blood CD34+ cells. Exp. Hematol. 31:789-797
Matsuura-Sawada R, Murakami T, Ozawa Y, et al. (2005). Reproduction of menstrual changes in transplanted human endometrial tissue in immunodeficient mice. Hum. Reprod. 20:1477-1484.
McCune JM, Namikawa R, Kaneshima H, Shultz LD, Lieberman M, Weissman IL (1988). The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science. 241:1632-1639.
McCune JM, Namikawa R, Shih CC, Rabin L, Kaneshima H (1990). Suppression of HIV infection in AZT-treated SCID/hu mice. Science. 247:564-566.
Mckenzie JI, Gan OI, Doedens M, Wang JCY, Dick JE (2006). Individual stem cells with highly variable proliferation and self-renewal properties comprise the human hematopoietic stem cell compartment. Nat. Immunol. 11:1225-1233.
Melkus MW, Estes JD, Padgett-Thomas A, et al. (2006). Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. Nat. Med. 12:1316-1322.
Mestas J, Hughes CC (2004). Of mice and not men: differences between mouse and human immunology. J. Immunol. 172:2731-2738.
Meuleman P, Libbrecht L, De Vos R, et al. (2005). Morphological and biochemical characterization of a human liver in a uPA-SCID mouse chimera. Hepatology. 41:847-856.
Miller RD, Hogg J, Ozaki JH, Gell D, Jackson SP, Riblet R (1995). Gene for the catalytic subunit of mouse DNA-dependent protein kinase maps to the scid locus. Proc. Natl. Acad. Sci. USA. 92:10792-10795.
Mitsumori K, Wakana S, Yamamoto S, Kodama Y, Yasuhara K, Nomura T, Hayashi Y, Maronpot RR (1997). Susceptibility of transgenic mice carrying human prototype c-Ha-ras gene in a short-term carcinogenicity study of vinyl carbamate and ras gene analyses of the induced tumors. Mol. Carcinog. 20(3):298-307.
Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE (1992). RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 68:869-877.
Mori N, Fujii M, Ikeda S, et al. (1999). Constitutive activation of NF-kappaB in primary adult T-cell leukemia cells. Blood. 93:2360-2368.
Mosier DE, Gulizia RJ, Baird SM, Wilson DB (1988). Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature. 335:256-259.
Mosier DE, Gulizia RJ, Baird SM, et al. (1989). Studies of HIV infection and the development of Epstein-Barr virus-related B cell lymphomas following transfer of human lymphocytes to mice with severe combined immunodeficiency. Curr. Top. Microbiol. Immunol. 152:195-199.
Mosier DE, Gulizia RJ, Baird SM, Wilson DB, Spector DH, Spector SA (1991). Human immunodeficiency virus infection of human-PBL-SCID mice. Science. 251:791-794.
Mosier DE, Gulizia RJ, MacIsaac PD, Torbett BE, Levy JA (1993). Rapid loss of CD4+ T cells in human-PBL SCID mice by noncytopathic HIV isolates. Science. 260:689-692.
Mota J, Rico-Hesse R (2009). Humanized mice show clinical signs of dengue fever according to infecting virus genotype. J. Virol. 83:8638-8645.
Muguruma Y, Yahata T, Miyatake H, et al. (2006). Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment. Blood. 107:1878-1887.
Nakamura M, Suemizu H (2008). Novel metastasis models of human cancer in NOG mice. Curr. Topics Microbiol. Immunol. 324:167-177.