Feline Models of the Gangliosidoses: Research Applications for Investigating the Pathogenesis of Lysosomal Storage Disease

Studies in recent years have demonstrated that ganglioside storage disease is characterized not only by lysosomal hydrolase deficiencies and concomitant storage of gangliosides, but also by specific changes in the structure of neurons such as meganeurite formation and aberrant dendritogenesis and synaptogenesis. The discovery of these unusual morphological alterations, unprecedented for mature neurons, has suggested new hypotheses relating to the pathogenesis of storage disorders, as well as to the functions of gangliosides in the normal nervous system. The availability of colony-reared feline models of GM,and GM2 gangliosidosis, which are near perfect analogues of these disorders in children, offers a unique opportunity to test these and other hypotheses related to neuronal dysfunction in these diseases. This paperreviews some of the characteristics of these models and their contributions made to date and, additionally, surveys some of the significant unanswered questions for future studies which are expected to contribute to a more complete understanding of the pathobiologyof neuronal storage disorders