INCREASED EXPRESSION OF CAVEOLIN-1 IN HETEROZYGOUS NIEMANN-PICK TYPE-II HUMAN FIBROBLASTS

Human Niemann-Pick type II fibroblasts, which encompass the panethnic type C (NPC) and Nova Scotia Acadian type D (NPD) variants, exhibit al tered expression of caveolin-1 protein when examined by immunoblotting using an anti-caveolin-1 monoclonal antibody. Unexpectedly, caveolin- 1 in heterozygous fibroblasts was significantly elevated as much as 10 -fold compared to caveolin-1 in normal and homozygous affected fibrobl asts, Homozygous NPC fibroblasts expressed caveolin-1 levels similar t o those in normal fibroblasts, while the expression of caveolin-1 in h omozygous NPD fibroblasts was slightly elevated. Northern analysis ind icates that normal fibroblasts and NPC heterozygous fibroblasts have s imilar amounts of caveolin-1 mRNA,while NPC homozygous fibroblasts hav e significantly less caveolin-1 mRNA. In contrast, heterozygous and ho mozygous NPD fibroblasts exhibit increased levels of caveolin-1 mRNA. These novel findings suggest that caveolin-1 containing subcellular st ructures are involved in the pathophysiology of Niemann-Pick type II d isease. Furthermore, altered caveolin-1 protein expression may serve a s a useful marker for the diagnosis of carriers of NPC or NPD. (C) 199 7 Academic Press.