Scientists began by compiling two "libraries" of more than 16,000 segments of nucleotide sequences (ESTs, or expressed sequence tags) of the genes that are present in enterocytes. The bioinformatics team, led by Nicholas Murgolo, Ph.D., senior principal scientist, Discovery Technologies and Bioinformatics, SPRI, used proprietary capabilities to explore publicly available genomics databases. The team focused their search on genes encoding proteins whose predicted structures suggested cell surface expression and potential interaction with cholesterol, two key characteristics that a protein involved in cholesterol absorption would likely possess. The scientists characterized and determined the function of a previously identified gene known as Niemann-Pick C1-Like 1 (NPC1L1) gene, whose name derives from its similarity to another gene that is mutated in individuals with the rare disorder Niemann-Pick disease. NPC1L1 has no role in Niemann-Pick disease.
Linking NPC1L1 to cholesterol absorption
Schering-Plough molecular biologists led by Scott Altmann, Ph.D., associate principal scientist, Cardiovascular/Metabolic Discovery Research, cloned the NPC1L1 gene and characterized its expression. Employing immunohistochemistry they showed that the NPC1L1 protein is specifically located on the brush border membranes of jejunal enterocytes, the side of the cell that comes in direct contact with the contents of the small intestine. The jejunum is the specific region of the small intestine where the majority of cholesterol absorption occurs.
To confirm the role of the newly identified protein in cholesterol ab
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Contact: Denise Foy
Denise.Foy@spcorp.com
908-423-7616
Schering-Plough Corporation
19-Feb-2004