Humanized Mouse Core
HUMANIZED MOUSE CORE (HMC) FACILITY
The humanized mouse (hu-mouse) model has revolutionized the ability to carry out in vivo studies of the human immune system. With over 10 years of experience developing hu-mouse models with functional human hematopoietic and lymphoid systems, we have pioneered novel humanized mouse models with robust, functional human immune systems [1-16]. Our original model has been replicated in many other laboratories (sometimes referred to as the “BLT” mouse). The application of this model has been pivotal in the exploration of human immune responses and disorders. Our expertise in this field was conducive to the development of other models, one of which gained renown as the Personalized Immune (PI) humanized mouse with the transplantation of patient-specific hematopoietic stem cells (HSCs) . Additionally, we have established protocols for humanized mice with human T cells that express tumor or viral antigen-specific TCRs as well as humanized mice that spontaneously develop autologous human leukemia by transplanting genetically manipulated HSCs.These refinements further expand the potential applications of the hu-mouse model. By providing our services to other laboratories, we aspire to support investigation of human immunology and expand our repertoire of hu-mouse models.
Core Services include breeding and maintenance of NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mouse colonies, construction of humanized mice, as well as confirmation of reconstitution of human hematopoietic and lymphoid systems by detection of >25% human cells (including T, B, and myeloid cells) in peripheral blood 8-10 weeks post-engraftment.
Standard Hu-Mouse (functional human immune system).
• Core provides standard hu-mice engrafted with human fetal Thymus + HSCs or HSCs only
• Core can construct hu-mice with specific transgenic backgrounds (HLA-A2, HLA-DQ8, hSGM3, etc.) to suit investigator’s needs
• Core can occasionally provide a few (<10) standard hu-mice for pilot express studies but we DO NOT regularly stockpile standard hu-mice
Personalized Immune (PI) Hu-Mouse (patient-specific human immune system)
• Investigators will provide patient specimens and HLA type the subjects
• Core will provide HLA-typed thymic tissue and construct PI mice
Customized Hu-Mouse (compromised human immune system)
• Core can provide hu-mice engrafted with virally transduced HSCs. Investigators are encouraged to provide their own transduced HSCs or viral vectors.
Additional Housing: $0.84/hu-mouse/day
CCTI: Columbia Center for Translational Immunology
DOM: Department of Medicine
Non-DOM: Other Departments
Please submit the Humanized Mouse Request Form at least 2 months prior to intended start date of hu-mouse reconstitution. Once hu-mice reconstitution has been confirmed (8-10 weeks), hu-mice are transferred to investigator’s mouse facility, unless Humanized Mouse Core (HMC) housing is required.
It is advised that interested investigators contact us before submission of the request form to thoroughly discuss project and options.
Humanized Mouse Core (HMC) Facility
BB-1516 William Black Building
Columbia Center for Translational Immunology
Columbia University Medical Center
650W, 168th Street, NY10032
Hui Wang MD, PhD
Tel: (212) 304-5565
Yong-guang Yang MD, PhD
Tel: (212) 304-5586
Megan Sykes, MD
Tel: (212) 304-5696
Our hu-mice related publications:
1. Lan, P., et al., Induction of human T-cell tolerance to porcine xenoantigens through mixed hematopoietic chimerism. Blood, 2004. 103(10): p. 3964-9.
2. Lan, P., et al., Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation. Blood, 2006. 108(2): p. 487-92.
3. Tonomura, N., et al., Antigen-specific human T-cell responses and T cell-dependent production of human antibodies in a humanized mouse model. Blood, 2008. 111(8): p. 4293-6.
4. Tonomura, N., et al., Pig islet xenograft rejection in a mouse model with an established human immune system. Xenotransplantation, 2008. 15(2): p. 129-35.
5. Kumar, P., et al., T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell, 2008. 134(4): p. 577-86.
6. Shimizu, I., et al., Comparison of human T cell repertoire generated in xenogeneic porcine and human thymus grafts. Transplantation, 2008. 86(4): p. 601-10.
7. Brainard, D.M., et al., Induction of robust cellular and humoral virus-specific adaptive immune responses in human immunodeficiency virus-infected humanized BLT mice. J Virol, 2009. 83(14): p. 7305-21.
8. Kim, S.S., et al., RNAi-mediated CCR5 silencing by LFA-1-targeted nanoparticles prevents HIV infection in BLT mice. Mol Ther, 2010. 18(2): p. 370-6.
9. Onoe, T., et al., Homeostatic expansion and phenotypic conversion of human T cells depend on peripheral interactions with APCs. J Immunol, 2010. 184(12): p. 6756-65.
10. Onoe, T., et al., Human natural regulatory T cell development, suppressive function, and postthymic maturation in a humanized mouse model. J Immunol, 2011. 187(7): p. 3895-903.
11. Hu, Z., N. Van Rooijen, and Y.G. Yang, Macrophages prevent human red blood cell reconstitution in immunodeficient mice. Blood, 2011. 118(22): p. 5938-46.
12. Hu, Z. and Y.G. Yang, Full reconstitution of human platelets in humanized mice after macrophage depletion. Blood, 2012. 120(8): p. 1713-6.
13. Bai, H., et al., Bcl-xL enhances single-cell survival and expansion of human embryonic stem cells without affecting self-renewal. Stem Cell Res, 2012. 8(1): p. 26-37.
14. Kalscheuer, H., et al., A model for personalized in vivo analysis of human immune responsiveness. Sci Transl Med, 2012. 4(125): p. 125ra30.
15. Huang, S.X., et al., Efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nat Biotechnol, 2014. 32(1): p. 84-91.
16. Rong, Z., et al., An effective approach to prevent immune rejection of human ESC-derived allografts. Cell Stem Cell, 2014. 14(1): p. 121-30.