The mousetrap: what we can learn when the mouse model does not mimic the human disease.

In recent years, mouse models for human metabolic diseases have become commonplace because the information gained from in vivo study of biochemical pathways is invaluable, and many metabolic diseases are relatively easy to recreate in mice through gene knockout technology in embryonic stem cells. In certain cases, however, the knockout mice may reproduce only some of the human disease phenotype, may be more severely affected than human cases, or may have no clinical phenotype at all. Under these circumstances, the disease pathology can become more complex, causing the researcher to evaluate basic differences in mouse and human biology as well as questions of genetic background, alternate pathways, and possible gene interactions. This review is a brief analysis of gene knockout models for Lesch-Nyhan syndrome, Lowe syndrome, X-linked adrenoleukodystrophy, Fabry disease, galactosemia, glycogen storage disease type II, metachromatic leukodystrophy, and Tay-Sachs disease, which produce a biochemical model of disease but often do not reproduce clinical symptoms. These mice may be useful for studying the biochemical and physiological pathways in which certain metabolites function toward embryonic and fetal development, as well as specific functions in various organs, and they may provide an inexpensive and useful model system for development of new therapeutic techniques.