A mutation in a mitochondrial transmembrane protein is responsible for thepleiotropic hematological and skeletal phenotype of flexed-tail (f/f) mice

We have studied the flexed-tail (f) mouse to gain insight into mammalian mi tochondrial iron metabolism. Flexed-tail animals have axial skeletal abnorm alities and a transient embryonic and neonatal anemia characterized by path ologic intramitochondrial iron deposits in erythrocytes, Mitochondrial iron accumulation is the hallmark of sideroblastic anemias, which typically res ult from defects in heme biosynthesis or other pathways that lead to abnorm al erythroid mitochondrial iron utilization. To clone the f gene, we used p ositional cloning techniques, and identified a frameshift mutation in a mit ochondrial transmembrane protein. The mutated gene, Sfxn1, is the prototype of a novel family of evolutionarily conserved proteins present in eukaryot es.