Dr. Leonard Shultz, "Humanized Mice" Pioneer

JAX® NOTES Issue 508, Winter 2008

Mice are not humans, but Leonard Shultz PhD of The Jackson Laboratory has been working for years to blur the differences. Because researching human biology in living humans is severely limited by ethical and technical constraints, Dr. Shultz has spent much of his research career constructing a succession of mouse models, each of which is more capable of simulating the human condition than the one before. Dr. Shultz's mouse-human chimaeras, or "humanized mice", are immunodeficient mice that either express human transgenes or can be engrafted with human tissue or cells, such as hematopoietic stem cells (HSCs) or peripheral-blood mononuclear cells (PBMCs). His most recent model, NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (005557), is arguably the most versatile immunodeficient mouse model available. This mouse lacks adaptive immune function and has multiple defects in innate immunity. Because it produces no functional B and T cells (even as it ages), has no natural killer (NK) cell activity, is resistant to lymphoma (a disease that plagues earlier models), and is long-lived, it can virtually be engrafted with a human immune system, making it a superior model for long-term HIV and other infectious disease research. Additionally, it does not need to be irradiated when used as a recipient of diabetic T cells in diabetes transfer experiments.

Dr. Shultz, along with Drs Dale Greiner and Fumihiko Ishikawa, recently co-authored a review discussing how generations of humanized mice have become powerful tools in pre-clinical testing and investigations of human biology (Shultz et al. 2007). The review includes the following content:

  • a history of the development of humanized mice, including a timeline and the names of the more notable models developed since the early 1980s,
  • descriptions of these notable models, and tables listing the advantages of each new model over its predecessors,
  • discussions on using these models in hematopoiesis, infectious and autoimmune disease, and regenerative medicine research, and
  • a discussion of some of the obstacles that must be overcome to produce the optimum humanized mouse of the future.

We distribute all the JAX® Mice models mentioned in Dr. Shultz's review. Additionally, JAX® Services offers many resources to help facilitate research involving humanized mice. To order mice or to inquire about JAX® Services, visit our Web site, or contact us at jaxservices@jax.org, 1-800-422-6423, or 1-207-288-5845.

Reference
(Author in bold is a Jackson Laboratory scientist.)

Shultz LD, Ishikawa F, Greiner DL. 2007. Humanized mice in translational biomedical research. Nat Rev Immunol 7:118-30.