A CELL-LINE DERIVED FROM SPHINGOMYELINOSIS MOUSE SHOWS ALTERATIONS IN INTRACELLULAR CHOLESTEROL-METABOLISM SIMILAR TO THOSE IN TYPE-C NIEMANN-PICK DISEASE

Cell lines derived from the sphingomyelinosis (gene symbol, spm) mouse were established from homozygous (spm/spm) and heterozygous (spm/ +) embryos according to a rigid 3T3 transfer schedule. The SPM-3T3 cells derived from a homozygous embryo showed extensive accumulation of intracellular cholesterol, attenuated esterification of exogenously added cholesterol and increased de novo cholesterol synthesis, when compared to SPMH-3T3 cells derived from a heterozygous embryo. The phenotypic abnormalities were very similar to those observed in fibroblasts from patients with Niemann-Pick disease type C (NP-C), in which a defect in the intracellular transport of unesterified cholesterol is suggested. The genetic defect in SPM-3T3 cells should be closely related to that in NP-C. The SPM-3T3 cell line is useful for biochemical and genetic studies on the regulation of intracellular cholesterol metabolism.