Gaucher disease, the result of inherited deficiency of glucocerebrosidase, is the most common lysosomal storage disease. No naturally occurring animal models are available for study of its pathophysiology or the development of new therapeutic strategies such as gene therapy. We describe an approach to gene targeting in embryonic stem cells to “knock out” glucocerebrosidase activity and generate a mouse line having the phenotype of severely affected infants with type 2 Gaucher disease. We also discuss an experiment in gene therapy using lethally irradiated mice that are reconstituted with murine fetal liver hematopoietic cells transduced with retrovirus encoding human glucocerebrosidase. Analyses of these animals show production of active human glucocerebrosidase in lysosomes of macrophages for at least 12 months after transplantation.

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Developmental Disabilities Research Reviews
Biophysical Genomics, Department Cell Biology & Genetics

McKinney, C., Sidransky, E., LaMarca, M., Riviere, I., Holleran, W., Martin, B., … Ginns, E. (1995). Gaucher disease: A tale of two species. Developmental Disabilities Research Reviews, 1(1), 79–86. doi:10.1002/mrdd.1410010114