Abstract
Mice with human hematopoietic system have become critical for research and preclinical studies. Mice with patient-derived xenografts of different tumors exist without human immune system. Answers can be addressed with the same immunodeficient mice that are chimeric for the human hemato-lymphoid system (humanized mice). The growing field of immune-oncology could benefit from preclinical studies with the humanized mice. Other fields will also benefit such as studies of infectious disease, regenerative medicine, organ transplant, and allergies. Here, we describe the method to humanize immune-deficient mice with human CD34+ hematopoietic cells.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Yong KSM, Her Z, Chen Q (2018) Humanized mice as unique tools for human-specific studies. Arch Immunol Ther Exp 66(4):245–266
Bosma GC, Custer RP, Bosma MJ (1983) A severe combined immunodeficiency mutation in the mouse. Nature 301(5900):527–530
Woodbine L, Neal JA, Sasi NK, Shimada M, Deem K, Coleman H, Dobyns WB, Ogi T, Meek K, Davies EG, Jeggo PA (2013) PRKDC mutations in a SCID patient with profound neurological abnormalities. J Clin Invest 123(7):2969–2980
Ailles LE, Gerhard B, Kawagoe H, Hogge DE (1999) Growth characteristics of acute myelogenous leukemia progenitors that initiate malignant hematopoiesis in nonobese diabetic/severe combined immunodeficient mice. Blood 94(5):1761–1772
Van der Loo JC, Hanenberg H, Cooper RJ, Luo FY, Lazaridis EN, Williams DA (1998) Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse as a model system to study the engraftment and mobilization of human peripheral blood stem cells. Blood 92(7):2556–2570
Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, Ueyama Y, Koyanagi Y, Sugamura K, Tsuji K, Heike T, Nakahata T (2002) NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood 100(9):3175–3182
Katano I, Ito R, Kamisako T, Eto T, Ogura T, Kawai K, Suemizu H, Takahashi T, Kawakami Y, Ito M (2014) NOD-Rag2null IL-2Rgammanull mice: an alternative to NOG mice for generation of humanized mice. Exp Anim 63(3):321–330
Shultz LD, Lang PA, Christianson SW, Gott B, Lyons B, Umeda S, Leiter E, Hesselton R, Wagar EJ, Leif JH, Kollet O, Lapidot T, Greiner DL (2000) NOD/LtSz-Rag1null mice: an immunodeficient and radioresistant model for engraftment of human hematolymphoid cells, HIV infection, and adoptive transfer of NOD mouse diabetogenic T cells. J Immunol 164(5):2496–2507
Andre MC, Erbacher A, Gille C, Schmauke V, Goecke B, Hohberger A, Mang P, Wilhelm A, Mueller I, Herr W, Lang P, Handgretinger R, Hartwig UF (2010) Long-term human CD34+ stem cell-engrafted nonobese diabetic/SCID/IL-2R gamma(null) mice show impaired CD8+ T cell maintenance and a functional arrest of immature NK cells. J Immunol 185(5):2710–2720
Wiekmeijer AS, Pike-Overzet K, Brugman MH, Salvatori DC, Egeler RM, Bredius RG, Fibbe WE, Staal FJ (2014) Sustained engraftment of cryopreserved human bone marrow CD34(+) cells in young adult NSG mice. Bioresources 3(3):110–116
Lim AI, Li Y, Lopez-Lastra S, Stadhouders R, Paul F, Casrouge A, Serafini N, Puel A, Bustamante J, Surace L, Masse-Ranson G, David E, Strick-Marchand H, Le Bourhis L, Cocchi R, Topazio D, Graziano P, Muscarella LA, Rogge L, Norel X, Sallenave JM, Allez M, Graf T, Hendriks RW, Casanova JL, Amit I, Yssel H, Di Santo JP (2017) Systemic human ILC precursors provide a substrate for tissue ILC differentiation. Cell 168(6):1086–1100. e10
Billerbeck E, Barry WT, Mu K, Dorner M, Rice CM, Ploss A (2011) Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor-, granulocyte-macrophage colony-stimulating factor-, and interleukin-3-expressing NOD-SCID IL2Rgamma(null) humanized mice. Blood 117(11):3076–3086
Van Lent AU, Dontje W, Nagasawa M, Siamari R, Bakker AQ, Pouw SM, Maijoor KA, Weijer K, Cornelissen JJ, Blom B, Di Santo JP, Spits H, Legrand N (2009) IL-7 enhances thymic human T cell development in “human immune system” Rag2−/-IL-2Rgammac−/− mice without affecting peripheral T cell homeostasis. J Immunol 183(12):7645–7655
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 106(51):21783–21788
Huntington ND, Legrand N, Alves NL, Jaron B, Weijer K, Plet A, Corcuff E, Mortier E, Jacques Y, Spits H, Di Santo JP (2009) IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. J Exp Med 206(1):25–34
Her Z, Yong KSM, Paramasivam K, Tan WWS, Chan XY, Tan SY, Liu M, Fan Y, Linn YC, Hui KM, Surana U, Chen Q (2017) An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia. J Hematol Oncol 10(1):162
Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367(6464):645–648
Lin S, Huang G, Cheng L, Li Z, Xiao Y, Deng Q, Jiang Y, Li B, Lin S, Wang S, Wu Q, Yao H, Cao S, Li Y, Liu P, Wei W, Pei D, Yao Y, Wen Z, Zhang X, Wu Y, Zhang Z, Cui S, Sun X, Qian X, Li P (2018) Establishment of peripheral blood mononuclear cell-derived humanized lung cancer mouse models for studying efficacy of PD-L1/PD-1 targeted immunotherapy. MAbs 10(8):1301–1311
Wang M, Yao LC, Cheng M, Cai D, Martinek J, Pan CX, Shi W, Ma AH, De Vere White RW, Airhart S, Liu ET, Banchereau J, Brehm MA, Greiner DL, Shultz LD, Palucka K, Keck JG (2018) Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy. FASEB J 32(3):1537–1549
Ito A, Ishida T, Yano H, Inagaki A, Suzuki S, Sato F, Takino H, Mori F, Ri M, Kusumoto S, Komatsu H, Iida S, Inagaki H, Ueda R (2009) Defucosylated anti-CCR4 monoclonal antibody exercises potent ADCC-mediated antitumor effect in the novel tumor-bearing humanized NOD/Shi-scid, IL-2Rgamma(null) mouse model. Cancer Immunol Immunother 58(8):1195–1206
Miyakawa Y, Ohnishi Y, Tomisawa M, Monnai M, Kohmura K, Ueyama Y, Ito M, Ikeda Y, Kizaki M, Nakamura M (2004) Establishment of a new model of human multiple myeloma using NOD/SCID/gammac(null) (NOG) mice. Biochem Biophys Res Commun 313(2):258–262
Bryce PJ, Falahati R, Kenney LL, Leung J, Bebbington C, Tomasevic N, Krier RA, Hsu CL, Shultz LD, Greiner DL, Brehm MA (2016) Humanized mouse model of mast cell-mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis. J Allergy Clin Immunol 138(3):769–779
Ito R, Maruoka S, Gon Y, Katano I, Takahashi T, Ito M, Izuhara K, Nunomura S (2019) Recent advances in allergy research using humanized mice. Int J Mol Sci 20(11):2740
Viehmann Milam AA, Maher SE, Gibson JA, Lebastchi J, Wen L, Ruddle NH, Herold KC, Bothwell AL (2014) A humanized mouse model of autoimmune insulitis. Diabetes 63(5):1712–1724
Gunawan M, Her Z, Liu M, Tan SY, Chan XY, Tan WWS, Dharmaraaja S, Fan Y, Ong CB, Loh E, Chang KTE, Tan TC, Chan JKY, Chen Q (2017) A novel human systemic lupus erythematosus model in humanised mice. Sci Rep 7(1):16642
Brehm MA, Jouvet N, Greiner DL, Shultz LD (2013) Humanized mice for the study of infectious diseases. Curr Opin Immunol 25(4):428–435
Munz C (2017) Humanized mouse models for Epstein Barr virus infection. Curr Opin Virol 25:113–118
Satheesan S, Li H, Burnett JC, Takahashi M, Li S, Wu SX, Synold TW, Rossi JJ, Zhou J (2018) HIV replication and latency in a humanized NSG mouse model during suppressive oral combinational antiretroviral therapy. J Virol 92(7):e02118–e02117
Amaladoss A, Chen Q, Liu M, Dummler SK, Dao M, Suresh S, Chen J, Preiser PR (2015) De novo generated human red blood cells in humanized mice support Plasmodium falciparum infection. PLoS One 10(6):e0129825
McIntosh BE, Brown ME, Duffin BM, Maufort JP, Vereide DT, Slukvin II, Thomson JA (2015) Nonirradiated NOD,B6.SCID Il2rgamma−/− Kit(W41/W41) (NBSGW) mice support multilineage engraftment of human hematopoietic cells. Stem Cell Rep 4(2):171–180
Acknowledgments
This work was supported by the following grants: Bosarge Family Foundation; In part by NAS and USAID, and that any opinions, findings, conclusions, or recommendations expressed in such article are those of the authors alone, and do not necessarily reflect the views of USAID or NAS.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Gergues, M., Ayer, S., Morelli, S., Greco, S.J., Rameshwar, P. (2021). Hematological Humanization of Immune-Deficient Mice. In: Singh, S.R., Hoffman, R.M., Singh, A. (eds) Mouse Genetics . Methods in Molecular Biology, vol 2224. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1008-4_14
Download citation
DOI: https://doi.org/10.1007/978-1-0716-1008-4_14
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-1007-7
Online ISBN: 978-1-0716-1008-4
eBook Packages: Springer Protocols