Humanized NSG mice
Despite the genetic similarities, differences between mice and humans can hinder their ability to support in vivo pharmacology studies that are human-specific (i.e. the molecule and/or pathway does not cross-react between mice and humans). We have been working on humanized mouse models generated by engraftment of immunodeficient mice with human immune cells.
We utilize the NOD scid IL2 receptor gamma chain knockout mice (NSG), constructed by JAX Professor Lenny Shultz, as the mouse host. NSG mice have been shown to support greater engraftment of human hematopoietic stem cells (hCD34+ cells) than all other strains (McDermott et al. 2010). These mice are a platform for studying hematopoiesis, inflammatory disease and human-specific pathogens, and help accelerate the development of potential therapies.
Study-ready cohorts of humanized mice are readily available for shipment to your institution— or customized drug efficacy studies in humanized mice can be executed by our In Vivo Services group. We routintely generate cohorts of NSG mice engrafted with hCD34+ cells, as well as the BLT model with HLA-restricted T cells and improved adaptive immunity. NSG mice engrafted with PBMCs are also available upon request.
Frequently Asked Questions
How is the human cell engraftment examined?
We examine the percentage of human CD45+ cells in the mouse peripheral blood by flow cytometry 12 weeks post engraftment (Figure 2). Published reports (Ishikawa et al. 2005) and our own experience suggest that it takes 12 weeks to reconstitute a functional human immune system in the engrafted NSG mice.
|Figure 2: Engraftment in peripheral blood of the NSG mouse. Peripheral blood was taken from mice 12 weeks post engraftment, analyzed by flow cytometry for the presence of human CD45+ cells and murine CD45+ cells. Enlarge graph||Figure 3: DTH response in humanized NSG. Mice engrafted from the same human donor were sensitized twice on the back with 0.2% DNFB, challenged 5 days later on the ear. Ear edema was measured by a digital caliper. Hydrocortisone was used as a reference compound. [Naive group did not receive DNFB sensitizeation; vehicle group was sensitized, but not challenged.] Enlarge graph|
What kind of mouse is delivered to customers?
Only mice with >25% human CD45+ cells in the peripheral blood 12 weeks post engraftment.
How functional is the engrafted human immune system in these mice?
The function of the engrafted immune system in the humanized NSG mice has been extensively reported in the literature. The list of publication is maintained on our website. We have established the delayed type hypersensitivity screening assay in the mice with >25% human CD45+ cells in the peripheral blood, suggesting the presence of a functional immune system (Figure 3). The BLT model has improved adaptive immune responses, including greater IgG production.
What is the health status of the mice?
The humanized NSG mice are maintained in the JAX In Vivo Services facility in Sacramento, CA. The room is operated as an intermediate barrier. The latest health report of the mouse room RB23 can be viewed here. Furthermore, the engrafted human hematopoietic stem cells have been tested to be free of HIV, HBV, HCV and LCMV (lymphocytic choriomeningitis virus).
Are there license requirements for the humanized NSG mice?
The Jackson Laboratory distributes NSG mice under an agreement with NIH. The NSG mice are available to non-profit research institutions under an MTA. Many companies already have a license that includes the engrafted NSG mice. To confirm that your company is covered or for new license inquiries, please contact:
Director, Technology Transfer
The Jackson Laboratory