Hepatic and extrahepatic expression of the new iron regulatory protein hemojuvelin.

BACKGROUND AND OBJECTIVES Hereditary hemochromatosis (HH) is a common disorder of iron overload. A rare variant of the disease, juvenile hemochromatosis, is an early-onset form which is caused by mutations in a recently identified gene, called HJV or HFE2. A previous report based on Northern blotting showed human HJV mRNA expression only in the skeletal muscle, liver and heart. DESIGN AND METHODS In this study we analyzed the expression of HJV mRNA in a number of human and mouse tissues by a sensitive reverse transcription-polymerase chain reaction method. We also studied the expression of HJV protein in mouse tissues using Western blotting. A polyclonal rabbit antibody was raised against a synthetic peptide which was designed based on the predicted sequence of human and mouse HJV protein. RESULTS Human HJV mRNA expression was detected in the liver, heart, esophagus, pancreas, descending colon, ileocecum and skeletal muscle. Mouse tissues that were positive for expression included brain, liver, heart, lung, stomach, spleen, kidney, duodenum, jejunum, ileum, colon, skeletal muscle, testis and blood. By Western blotting, HJV protein expression was detected in the mouse liver, heart, kidney, brain and muscle. INTERPRETATION AND CONCLUSIONS The facts that HJV protein is expressed in the liver and mutations in the HJV gene induce hepatic iron accumulation point to a possibility that HJV protein may modulate iron transport in hepatocytes. The wide expression of HJV as shown in the present study suggests that its role in regulating iron allocation could be extended to other tissues beyond the liver.