Alternate splicing produces a soluble form of the hereditary hemochromatosis protein HFE

HFE is a non-typical MHC class 1-type protein that is mutated in hereditary hemochromatosis. The purpose of this study was to identify possible splice variants of HFE mRNA and investigate the regulation of these isoforms in d uodenum and liver of patients with normal and altered iron stores. RT-PCR w as performed using HFE specific primers and duodenal RNA obtained from pati ents with hemochromatosis, iron deficiency, secondary iron overload and nor mal controls. The reaction products were visualized by Southern blot and id entified by DNA sequence analysis. Additional studies were performed on RNA isolated from liver and a range of human tissues. A truncated (soluble) fo rm of HFE protein was identified that lacks the transmembrane domain and oc curs as a result of alternative splicing. Soluble HFE was found predominant ly in the duodenum, spleen, breast, skin and testicle. In hereditary hemoch romatosis full length HFE was the predominant isoform present in the duoden um similar to iron deficiency. Alternate splicing produces soluble HFE that may have a unique function to regulate cellular iron transport. (C) 1999 A cademic Press.