Allogeneic bone marrow-plus-liver transplantation in the C57BL/KsJ spm/spm mouse, an animal model of Niemann-Pick disease.

The C57BL/KsJ spm/spm mouse, an animal model of Niemann-Pick disease, shows defective sphingomyelinase activity resulting in accumulation of sphingomyelin in various organs. To replace the defective enzyme, allogeneic bone marrow-plus-liver transplantation was performed. Bone marrow transplantation with or without concomitant liver grafting in C57BL/KsJ spm/spm mice at the age of 2-9 weeks led to an amelioration of the hepatosplenomegaly. The treatment, however, neither prevented the development of neurological signs nor increased the life-span. The sphingomyelin and cholesterol contents of the liver decreased, while sphingomyelinase activity in the liver increased after bone marrow transplantation. Foam cells disappeared from the bone marrow, liver, spleen, thymus, and lymph nodes, but depletion of Purkinje cells was not prevented. These results suggest that bone marrow transplantation either alone or with liver transplantation may become a useful strategy for the treatment of Niemann-Pick disease provided the central nervous system is not involved.