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

摘要: Abstract Objective: Bone marrow transplantation has been shown to alleviate symptoms outside the CNS in many lysosomal storage diseases depending on type and stage of disease, but effect neurological is variable or still unclear. Aspartylglucosaminuria (AGU) a disease characterized by mental retardation, recurrent infections childhood, hepatosplenomegaly coarse facial features. Vacuolized lysosomes are found all tissues patients uncleaved enzyme substrate excreted urine. The recently generated AGU mouse model closely mimicks human serves as good study efficiency bone this disease. Methods: Eight-week-old mice were lethally irradiated transplanted with from normal donors. AGA activity was measured liver brain degree correction tissue pathology analyzed light electron microscopy. Reverse (AGU wild-type mice) also performed. Results: Six months after 13% liver, only 3% brain. Tissue reversed spleen, not kidney. urinary excretion diminished detectable. No vacuoles reverse transplantation, subtle detected Conclusion: Liver spleen corrected there no accumulation kidneys.