Correction of peripheral lysosomal accumulation in mice with aspartylglucosaminuria by bone marrow transplantation

Objective: Bone marrow transplantation has been shown to alleviate symptoms outside the CNS in many lysosomal storage diseases depending on the type a nd stage of the disease, but the effect on neurological symptoms is variabl e or still unclear. Aspartylglucosaminuria (AGU) is a lysosomal storage dis ease characterized by mental retardation, recurrent infections in childhood , hepatosplenomegaly and coarse facial features. Vacuolized storage lysosom es are found in all tissues of patients and uncleaved enzyme substrate is e xcreted in the urine. The recently generated AGU mouse model closely mimick s the human disease and serves as a good model to study the efficiency of b one marrow transplantation in this disease. Methods: Eight-week-old AGU mic e were lethally irradiated and transplanted with bone marrow from normal do nors. The AGA enzyme activity was measured in the liver and the brain and t he degree of correction of tissue pathology was analyzed by light and elect ron microscopy. Reverse bone marrow transplantation (AGU bone marrow to wil d-type mice) was also performed, Results: Six months after transplantation the AGA enzyme activity was 13% of normal in the liver, but only 3% in the brain. Tissue pathology was reversed in the liver and the spleen, but not i n the brain and the kidney. The urinary excretion of enzyme substrate was d iminished but still detectable. No storage vacuoles were found in the tissu es after reverse transplantation, but subtle excretion of uncleaved substra te was detected in the urine. Conclusion: Liver and spleen pathology of AGU was corrected by bone marrow transplantation, but there was no effect on l ysosomal accumulation in the CNS and in the kidneys, (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.