Niemann-Pick type C (NPC) is an autosmal-recessive, neurovisceral disorder that is marked by neurological decline (progressive cognitive impairment, ataxia, dystonia, dysphagia, dysarthria, seizures, cataplexy and dementia) and hepatosplenomegaly resulting from cholesterol lipidosis. The gene (NPC-1) that is mutated in NPC was recently cloned and was found to be a membrane protein of unknown function but possibly involved in cholesterol homeostasis due to the presence of a sterol-sensing domain sequence in the protein. In order to study the function and role of the protein in cholesterol trafficking and homeostasis, we have succesfully generated 6 polyclonal antibodies against various segments of the protein. These antibodies are being used to identify subcellular localization of the NPC1 protein and to study its activity in the presence or absence of cholesterol. In addition, the NPC1 protein showed sequence homologies to worm (C. elegans) sequences. To exploit the worm system, null mutants were generated by EMU mutagenesis. The two homologous genes in worms have been successfully targeted and are now being characetrized for abnormal phenotype.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Intramural Research (Z01)
Project #
1Z01HG000084-03
Application #
6109004
Study Section
Special Emphasis Panel (LGT)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
National Human Genome Research Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code