A second complementation class of cholesterol transport mutants with a variant Niemann-Pick type C phenotype.

We previously isolated Chinese Hamster ovary cell mutants that were defective in the intracellular transport of low density lipoprotein (LDL)-derived cholesterol (Dahl, N.K., K.L. Reed, M.A. Daunais, J.R. Faust, and L. Liscum. 1992 J. Biol. Chem. 267: 4889-4896). Several of the mutants exhibited the same biochemical phenotype as classical Niemann-Pick type C (NPC) fibroblasts. Complementation analysis between these mutants and other cholesterol transport mutants with a variant biochemical phenotype has defined two complementation classes. One class is characterized by expression of the classical NPC phenotype and may represent a true cholesterol transport mutant, while the second is characterized by expression of a variant NPC phenotype and may represent a signaling defect in LDL-sensitive homeostatic responses.