Human Immune System Mouse Resources

Investigators submitting applications in response to an HU CFAR Developmental & Mentoring Core RFP for studies involving the use of humanized mice may request additional funding to access humanized mice through the HISM Core at the Ragon Institute of MGH, MIT and Harvard. Details are provide in each RFP released. More information about the HISM Core is provided below.

Services: The HU CFAR, through the Human Immune System Mouse Core at the Ragon Institute of MGH, MIT and Harvard, offers several different versions of humanized mice, useful for a broad array of investigations into human disease. For collaborating investigators, the Core will generate humanized mice, perform models of human diseases (most commonly but not exclusively HIV infection), and acquire blood and tissue samples, as directed by collaborating investigators, for transfer and analyses in their laboratories.

  • Humanized mouse models provided:
    • BLT (Bone Marrow-Liver-Thymus) mice: These mice are generated by adoptive transfer of human CD34+ stem cells, and transplantation of autologous human thymic grafts, into immunodeficient mice. This version of humanized mice have the most functional human immune systems, and is illustrated in the article by Brainard, et al.
    • Hu-HSC mice: These mice are generated by adoptive transfer of human CD34+ stem cells into immunodeficient mice.
    • Hu-PBL mice: These mice are generated by adoptive transfer of human peripheral blood leukocytes into immunodeficient mice.
    • Hu-CD4+ mice: These mice are generated by adoptive transfer of purified human CD4+ T cells into immunodeficient mice.
    • Potential collaborating investigators are encouraged to contact the Core Director and/or Associate Director to discuss which model(s) will best serve their experimental needs.

Publications:  A list of publications the HMP has collaborated on can be found here: http://www.ncbi.nlm.nih.gov/pubmed/?term=tager+am%5Bau%5D+humanized+mouse

Because the Ragon Human Immune System Mouse Core Director and Associate Director work closely with investigators in the design, performance, analyses and description of all humanized mouse experiments, we ask to be recognized as co-authors on publications including these experiments.

For more detailed information on the Human Immune System Mouse Core Program, please refer to http://ragoninstitute.org/research/services/humanized-mouse.

Despite great effort, an ideal animal model in which to study HIV pathogenesis and test vaccine efficacy remains elusive. Recently, we and others have developed a markedly improved humanized mouse model of HIV by transplanting human CD34+ stem cells and autologous human thymic grafts into immunodeficient mice (see the article Brainard DM et al. Induction of robust cellular and humoral virus-specific adaptive immune responses in human immunodeficiency virus-infected humanized BLT mice).

In this model, we have achieved robust repopulation of mouse lymphoid tissues with human immune cells, and have generated robust anti-HIV cellular and humoral immune responses in these humanized mice. We believe this improved humanized mouse model will allow us to study questions regarding the biology of HIV-1 not readily approachable through human studies.

The Ragon Human Immune System Mouse Core was established in order to further develop this model, and to make it available to the wider research community, both locally and globally.  Highly experienced personnel produce these animals and perform experiments in collaboration with HU CFAR investigators and investigators at other CFARs, as well as in collaboration with non-CFAR HIV investigators throughout the USA and countries around the world.