Complementation studies in human and feline Niemann-Pick type C disease

Complementation studies were performed to determine if the gene responsible for the major form of human Niemann-Pick type C disease (NPC) and a feline model of NPC are orthologous. Cell fusions between human NPC and feline NP C fibroblasts were conducted to assess whether the multinucleated heterokar yons that were formed showed a reversal of the NPC phenotype. Cultured fibr oblasts from NPC-affected humans and NPC-affected cats were hybridized and then analyzed for complementation by challenging the cells with low-density lipoprotein (LDL) and subsequently staining with the fluorescent antibioti c filipin to visualize any abnormal accumulation of unesterified cholestero l. All of the multinucleated cells formed from these fusions retained the N PC staining phenotype, indicating an absence of complementation and suggest ing that the underlying defect in the major form of human NPC and this feli ne model of NPC involve orthologous genes, (C) 1999 Academic Press.