A mutation in a mitochondrial transmembrane protein is responsible for the pleiotropic hematological and skeletal phenotype of flexed-tail (f/f) mice
A mutation in a mitochondrial transmembrane protein is responsible for the pleiotropic hematological and skeletal phenotype of flexed-tail (f/f) mice
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DOI：
10.1101/gad.873001
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发表时间：
2001-03-15
影响因子：
10.5
通讯作者：
Andrews, NC
中科院分区：
文献类型：
--
作者：
Fleming, MD;Campagna, DR;Andrews, NC
我们对弯曲尾巴(F)小鼠进行了研究，以深入了解哺乳动物的线粒体铁代谢。屈尾动物具有中轴性骨骼异常和短暂的胚胎和新生儿贫血，其特征是红细胞中病理性的线粒体内铁沉积，线粒体铁积聚是铁粒细胞性贫血的特征，通常是由于血红素生物合成缺陷或其他导致红系线粒体铁利用异常的途径所致。为了克隆f基因，我们使用了定位克隆技术，并在线粒体跨膜蛋白中鉴定了一个移码突变。突变的基因Sfxn1是真核生物中存在的一个新的进化保守蛋白家族的原型。
We have studied the flexed-tail (f) mouse to gain insight into mammalian mitochondrial iron metabolism. Flexed-tail animals have axial skeletal abnormalities and a transient embryonic and neonatal anemia characterized by pathologic intramitochondrial iron deposits in erythrocytes, Mitochondrial iron accumulation is the hallmark of sideroblastic anemias, which typically result from defects in heme biosynthesis or other pathways that lead to abnormal erythroid mitochondrial iron utilization. To clone the f gene, we used positional cloning techniques, and identified a frameshift mutation in a mitochondrial transmembrane protein. The mutated gene, Sfxn1, is the prototype of a novel family of evolutionarily conserved proteins present in eukaryotes.