The goal of this project is to develop a therapeutic agent for the treatment of obesity. Obesity is a public health problem in our society associated with psychological and medical morbidities. Recently, a murine gene encoding the obese (ob) gene product was isolated. Evidence exists that the ob gene product is a satiety factor. In Phase l, the murine target tissues for ob gene product will be identified by autoradiography with radiolabelled ob gene product. A cDNA library will be constructed from the identified target tissue. Multiple expression cloning strategies will be employed to clone the cDNA of the receptor for ob gene product, these include; cloning by panning, autoradiographic emulsion, and affinity enrichment. The murine gene will be used to isolate the cDNA encoding the human ob gene product receptor. Obtaining the cDNA encoding the human ob gene product receptor in Phase l, will provide an essential reagent for the pharmaceutical discovery program of Phase II. Phase III will involve determination of the final form of the satiety drug. Animal and clinical trials will be performed to demonstrate safety and efficacy.
