Humanized Mouse Services
 
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Generation of humanized BLT mice by transplanting human CD34+ stem cells and autologous human thymic grafts into immunodeficient mice.

  Collection of blood samples and performance of flow cytometry on peripheral blood leukocytes of the BLT mice to characterize their human immune reconstitution prior to use.
  HIV infection of humanized BLT mice.
  Handling of, and specimen collection from, HIV-infected mice. Specimens collected can include blood, spleen, lymph nodes, bone marrow, lung, liver, GI tract and GU tract.
  Further characterization of the human virus-specific cellular and humoral immune responses generated in HIV-infected BLT mice, to expand the areas of investigation this model can support.
Eligibility
Eligibility for use of mice generated by the Ragon Institute Humanized Mouse Program will be limited to investigators who are either Ragon Institute faculty members, or who have received funding through the Ragon Institute (via Innovation Awards, Fellowship Awards, Pilot Awards, or Program funding)
Getting Started

Eligible Ragon Institute investigators who are interested in working with the Humanized Mouse Program will be asked to submit a Concept Sheet describing their proposed project. Concept sheet templates are available for download here.

Interested investigators will be asked to describe their proposed study’s hypothesis, specific aim(s), background, rationale and preliminary results, and experimental design. Investigators will also be asked to indicate the number of mice required, and identify a funding source for the project.

Availability of Mice

The Humanized Mouse Program will generate approximately 430 BLT mice per year to support Ragon activities. Of these 430 mice, approximately 100 will be used for the Program’s activities to improve the BLT model and validate its capacity to assess HIV vaccine candidates. The remaining approximately 330 BLT mice will be used to support the collaborative studies of eligible Ragon investigators. We envision supporting 5 to 8 Ragon collaborators/year with 40 to 80 BLT mice/project/year.
Pritoritization of Projects

Concept sheets will be reviewed and priority scores assigned by a review committee including the Directors of the Humanized Mouse Program and members of the Ragon Institute Steering Committee. The review committee will meet twice per year to rank concepts submitted in the prior six-month period.

Those projects receiving the highest priority scores will be allocated mice pending Institutional Animal Care and Use Committee (IACUC) approval of the specific experiments proposed. Program personnel, with the input of the collaborating investigators, will submit an IACUC amendment to the Program’s approved “blanket” protocol, describing the experiments to be performed in each individual project selected to be performed by the Program Review Committee (see additional information about IACUC approvals below).

Animal Protocols

The humanized mouse platform has an active “blanket” Institutional Animal Care and Use Committee (IACUC) protocol that covers the generation of the BLT mice, and outlines the general framework of most types of experiments anticipated, e.g. assessments of candidate vaccine immunogenicity and/or efficacy, assessments of the efficacy of novel anti-viral therapeutics, and assessments of the effects of the genetic manipulation of human hematopoietic stem cells prior to use to generate BLT mice. Each individual project selected to be performed will require IACUC approval of an amendment to the Program’s protocol. Program personnel, with the input of the collaborating investigator(s), will submit the required amendment to describe the specific experiments that will be performed as part of that individual project.

Because of the complexity of the model, the desire to maintain consistency, and the experience required for the safe handling of HIV-infected animals, IACUC protocols will be held by the Program’s directors, BLT mice will be housed in the Program’s facilities, and will be handled by the Program’s personnel. If collaborating investigators wish to house and handle BLT mice in their own animal facilities, potential exceptions to these policies can be discussed with the Program directors on a case-by-case basis.