Vujić Spasić Maja, Kiss Judit, Herrmann Thomas, Galy Bruno, Martinache Stefanie, Stolte Jens, Gröne Hermann-Josef, Stremmel Wolfgang, Hentze Matthias W, Muckenthaler Martina U
Department of Pediatric Oncology, Hematology and Immunology, University Hospital of Heidelberg, 69120 Heidelberg, Germany.
Cell Metab. 2008 Feb;7(2):173-8. doi: 10.1016/j.cmet.2007.11.014.
Hereditary hemochromatosis (HH) is a prevalent, potentially fatal disorder of iron metabolism hallmarked by intestinal hyperabsorption of iron, hyperferremia, and hepatic iron overload. In both humans and mice, type I HH is associated with mutations in the broadly expressed HFE/Hfe gene. To identify where Hfe acts to prevent HH, we generated mice with tissue-specific Hfe ablations. This work demonstrates that local Hfe expression in hepatocytes serves to maintain physiological iron homeostasis, answering a long-standing question in medicine and explaining earlier clinical observations.
遗传性血色素沉着症（HH）是一种常见的、可能致命的铁代谢紊乱疾病，其特征为肠道铁吸收过多、高铁血症和肝脏铁过载。在人类和小鼠中，I型HH都与广泛表达的HFE/Hfe基因突变有关。为了确定Hfe在预防HH中发挥作用的位置，我们构建了组织特异性Hfe基因敲除小鼠。这项研究表明，肝细胞中的局部Hfe表达有助于维持生理铁稳态，回答了医学上一个长期存在的问题，并解释了早期的临床观察结果。
