Lessons learnt from animal models: pathophysiology of neuropathic lysosomal storage disorders

Abstract

Approximately 50 inborn errors of metabolism known as lysosomal storage disorders have been discovered to date, most of which are due to a single mutation in a gene encoding a soluble lysosomal enzyme. Consequently, inadequate enzyme activity results in the accumulation of substrates for that enzyme, invariably accompanied by a wide variety of secondary pathological changes. Many of these conditions remain untreatable, and therefore, research into pathogenic processes and potential treatment strategies is intense. A key tool for researchers in this area is the availability of clinically relevant animal models in which to study disease manifestation and evaluate therapeutic outcomes. Large numbers of both naturally occurring and genetically modified animal models of neurodegenerative lysosomal storage disorders are in existence, with spontaneous models occurring in both large domestic (e.g., cat, dog, sheep) and small (e.g., mouse) animal species. Many have undergone rigorous phenotypic characterization and are now providing us with insights into neurological disease processes. The purpose of this review is to highlight some of the major lessons learnt from these studies.