Mucopolysaccharidosis type VII in the developing mouse fetus

Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease cau sed by a deficiency of beta-glucuronidase (1). MPS VII is a fatal, progress ive degenerative disorder, and a number of patients die of hydrops fetalis. Thus an approach to treating this disease may be by transplantation or gen e therapy in utero. A mouse model of MPS VII has been studied extensively b ut the disease in affected fetal mice has not been characterized, which is essential for evaluation of therapeutic efficacy. Fetal and newborn mice af fected with MPS VII were examined for lysosomal enzyme activities and for t he presence of typical storage lesions in comparison to normal and carrier littermates. No beta-glucuronidase enzymatic activity was detected in any o f the tissues of affected mice, indicating that transplacental transfer of beta-glucuronidase from the dam did not occur. Lesions were not detected in affected fetuses of 13.5 d gestational age on light or electron microscopy . Vacuolation in cells, typical of lysosomal accumulation of substrate, was first seen in a small number of cells of the reticulo-endothelial system i n 15.5 d gestational age livers and in 18.5 d gestational age brains. Stora ge lesions were not seen consistently in endothelial and Kupffer cells of f etal livers until 18.5 d gestational age and in brains until birth. The res ults suggest that treatment of affected mice performed at 13.5 d gestationa l age may be effective in forestalling disease manifestations.