The SCID mouse: relevance as an animal model system for studying human disease

The simultaneous description some 5 years ago of two methods for the partial reconstitution of a human immune system in severe combined immune-deficient (SCID) mice (collectively, human:SCID mice) was met with great enthusiasm. At the time, it was hoped that human:SCID mice would provide experimental animal model systems for studying human disease and the human immune system. Many of these hopes have been borne out. Importantly, the experimental results obtained from these chimeric human/animal studies appear to be relevant to human disease and immune function. In spite of these glowing achievements, the SCID mouse may not represent the optimal experimental system with which to address these questions. The incomplete penetrance ("leakiness") of the scid mutation and the recent discovery that the mutation is not lymphoid specific, but rather affects a general DNA repair pathway, will only serve to complicate the interpretation of already complex biological interactions. Recently other immune-deficient mice have been described that appear to overcome one or both of these problems and thus these mice could represent improved hosts for the adaptive transfer of a human immune system. The current status of the SCID mouse in light of these new findings is discussed.