Wang Kun, Zhou Bing, Kuo Yien-Ming, Zemansky Jason, Gitschier Jane
Howard Hughes Medical Institute and Department of Medicine, University of California, San Francisco, 94143, USA.
Am J Hum Genet. 2002 Jul;71(1):66-73. doi: 10.1086/341125. Epub 2002 May 24.
The rare inherited condition acrodermatitis enteropathica (AE) results from a defect in the absorption of dietary zinc. Recently, we used homozygosity mapping in consanguineous Middle Eastern kindreds to localize the AE gene to an approximately 3.5-cM region on 8q24. In this article, we identify a gene, SLC39A4, located in the candidate region and, in patients with AE, document mutations that likely lead to the disease. The gene encodes a histidine-rich protein, which we refer to as "hZIP4," which is a member of a large family of transmembrane proteins, some of which are known to serve as zinc-uptake proteins. We show that Slc39A4 is abundantly expressed in mouse enterocytes and that the protein resides in the apical membrane of these cells. These findings suggest that the hZIP4 transporter is responsible for intestinal absorption of zinc.
罕见的遗传性疾病肠病性肢端皮炎（AE）是由膳食锌吸收缺陷引起的。最近，我们利用近亲中东家族的纯合性定位，将AE基因定位到8q24上一个约3.5厘摩的区域。在本文中，我们鉴定出位于候选区域的一个基因SLC39A4，并在AE患者中记录了可能导致该疾病的突变。该基因编码一种富含组氨酸的蛋白质，我们将其称为“hZIP4”，它是一个跨膜蛋白大家族的成员，其中一些已知可作为锌摄取蛋白。我们发现Slc39A4在小鼠肠细胞中大量表达，且该蛋白位于这些细胞的顶端膜上。这些发现表明hZIP4转运蛋白负责肠道对锌的吸收。
