JAX Notes January 01, 2008

Dr. Leonard Shultz, ‘humanized mice’ pioneer

Leonard Shultz, Ph.D.

Mice are not humans, but Leonard Shultz, Ph.D., 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).

One of his landmark models, 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.

In 2007, Dr. Shultz, along with Drs. Dale Greiner and Fumihiko Ishikawa, 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:

  • a history of the development of humanized mice, including the more notable models developed since the early 1980s
  • descriptions of models and tables listing the advantages of each model over its predecessors
  • using these models in hematopoiesis, infectious, autoimmune disease, and regenerative medicine research
  • 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.

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.