Production and characterization of a monoclonal antibody against Niemann Pick type C protein

Niemann Pick type C is a severe, incurable disease caused, in the majority of cases, by mutations in the Niemann Pick type C protein 1 (NPC1). The pathology and biochemical changes associated with the disease have been extensively studied. However, the function of the protein is still unknown, and recent studies challenge the established concept that a defect in cholesterol and sphingolipids transport is the primary cause of this human lipidosis. Clearly defining the mechanisms by which defects in this protein lead to the disease phenotype will require further studies on the structure and function of this protein. Therefore, the development of a well-characterized monoclonal antibody (MAb) against this protein to facilitate such studies is an important goal. Here, we describe the production and characterization of such a MAb. The antibody is demonstrated to be highly specific and species cross-reactive. Function studies show that the antibody induces the NPC1 disease phenotype in cells, making it highly likely that the antibody blocks function of the NPC1 protein.