A Chimeric Mouse Model of Gaucher Disease

BACKGROUND: There is a major need for a mouse model of Gaucher disease, but the glucocerebrosidase knockout mouse is not viable; it dies shortly before or immediately after birth, apparently because of involvement of the central nervous system and/or skin. The most common form of Gaucher disease, type I, has a phenotype that is limited to the monocyte-macrophage system. MATERIALS AND METHODS: We have created a chimeric mouse by infusing hematopoietic stem cells from fetuses that are homozygous for the glucocerebrosidase knockout into irradiated mice. RESULTS: The chimeric mice manifested a severe deficiency of glucocerebrosidase activity in peripheral blood cells and spleen indicating a lack of cell-cell correction. Levels of glucocerebroside in spleen and liver are increased, and infusing the mice with exogenous glucocerebroside/albumin particles produced a marked increase in the amount of glucocerebroside stored in liver and spleen. Morphologically identifiable Gaucher cells were not present. CONCLUSIONS: The chimeric model reflects the increased glycolipid storage in the reticuloendothelial system that is characteristic of Gaucher disease, and could be useful as a model for studying treatment of Gaucher disease.