Cholesterol transport gene

Abstract

Methods and compounds are disclosed for lowering serum LDL levels or serum cholesterol levels, or for reducing the transport of cholesterol from the gut to the blood or the lymph, based on the observation that a gene known as ABC1 is necessary in order for cholesterol to be transported from the intestinal lumen into the bloodstream. A mutant chicken phenotype, known as the WHAM chicken, characterized by low levels of serum LDL and reduced transport of cholesterol, facilitated the discovery of this function of the ABC1 gene. Techniques which act to inhibit ABC1 activity in the cells of the intestinal wall will result in lower serum cholesterol.

1 .- 7 . (canceled)  
     
     
         8 . A method for identifying drugs that can lower serum cholesterol levels comprising assaying the drug to test if it can bind to an ABC1 protein.  
     
     
         9 .- 11 . (canceled)  
     
     
         12 . A screening assay for determining whether a candidate compound is useful for reducing transport of cholesterol from the gut to the blood or lymph, or for lowering LDL or serum cholesterol levels comprising 
 (a) providing an assay system having a measurable ABC1 biological activity;    (b) contacting the assay with the candidate compound; and    (c) measuring ABC1 biological activity,    wherein modulation of ABC1 biological activity, relative to an assay not contacted with the candidate compound, indicates that the candidate compound is useful for the treatment of said disease or condition.    
     
     
         13 . The screening assay of  claim 12  wherein the assay system is a cell based system  
     
     
         14 . The screening assay of  claim 12  wherein the assay system is a cell free system.  
     
     
         15 . (canceled)  
     
     
         16 . A screening assay for determining whether a candidate compound has the ability to reduce transport of cholesterol from the gut to the blood or lymph, or to lower LDL or serum cholesterol levels, said screening assay comprises the steps of: 
 (a) providing a cell expressing an ABC1 gene or a fragment thereof;    (b) contacting said cell with said candidate compound; and    (c) measuring ABC1 activity of said cell,    wherein altered ABC1 activity, relative to a cell not contacted with said compound, indicates that said candidate compound has said ability.    
     
     
         17 .- 21 . (canceled)