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

Abstract

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.

• Authors: M D Fleming, D R Campagna, J N Haslett, C C Trenor 3rd, N C Andrews
• Journal: Genes & development (Genes Dev) Vol. 15 Issue 6 Pg. 652-7 (Mar 15 2001) ISSN: 0890-9369 [Print] United States
• PMID: 11274051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cation Transport Proteins
• DNA, Complementary
• Membrane Proteins
• Sfxn1 protein, mouse

Topics

• Amino Acid Sequence
• Animals
• Blotting, Northern
• Blotting, Western
• Bone and Bones (abnormalities)
• Cation Transport Proteins
• Cell Line
• Cell Membrane (metabolism)
• Cloning, Molecular
• DNA Mutational Analysis
• DNA, Complementary (metabolism)
• Frameshift Mutation
• Humans
• Membrane Proteins (biosynthesis, genetics)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Mitochondria (metabolism)
• Models, Genetic
• Molecular Sequence Data
• Open Reading Frames
• Phenotype
• Physical Chromosome Mapping
• Sequence Homology, Amino Acid
• Tissue Distribution