Mouse Models of Human Lysosomal Diseases

Genetically authentic animal models of human lysosomal diseases occur spontaneously in many mammalian species. However, most are among larger domestic or farm animals with only two well-defined genetic lysosomal diseases known among rodents. This status changed dramatically in recent years with the advent of the combined homologous recombination and embryonic stem cell technology, which allows directed generation of mouse models that are genetically equivalent to human diseases. Almost all known human sphingolipidoses, two mucopolysaccharidoses and aspartylglycosaminuria have so far been duplicated in mice and more are expected in the near future. This technology also allows generation of mouse mutants that are not known or are highly unlikely to exist in humans, such as "double-knockouts." These animal models will play an important role in studies of the pathogenesis and treatment of these disorders. While the utility of these mouse models is obvious, species differences in brain development and metabolic pathways must be always remembered, if the ultimate goal of the study is application to human patients.