Iron metabolism mutant hbd mice have a deletion in Sec15l1, which has homology to a yeast gene for vesicle docking

Defects in iron absorption and utilization lead to iron deficiency and anemia. While iron transport by transferrin receptor-mediated endocytosis is well understood, it is not completely clear how iron is transported from the endosome to the mitochondria where heme is synthesized. We undertook a posi...

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Bibliographic Details
Published in:Genomics (San Diego, Calif.) Calif.), 2005-12, Vol.86 (6), p.668-673
Main Authors: White, Robert A., Boydston, Leigh A., Brookshier, Terri R., McNulty, Steven G., Nsumu, Ndona N., Brewer, Brandon P., Blackmore, Krista
Format: Article
Language:English
Subjects:
Anemia
Anemia, Iron-Deficiency - genetics
Animals
Base Sequence
Biological and medical sciences
Chromosome aberrations
Chromosome Mapping
Cloning, Molecular
DNA Mutational Analysis
Endocytosis - genetics
Exons - genetics
Fundamental and applied biological sciences. Psychology
Gene Expression
Genes. Genome
Genetics of eukaryotes. Biological and molecular evolution
Iron - metabolism
Medical genetics
Medical sciences
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Mice, Mutant Strains
Molecular and cellular biology
Molecular genetics
Molecular Sequence Data
Mouse mutant
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
Sequence Deletion - genetics
Transport Vesicles - metabolism
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Summary:Defects in iron absorption and utilization lead to iron deficiency and anemia. While iron transport by transferrin receptor-mediated endocytosis is well understood, it is not completely clear how iron is transported from the endosome to the mitochondria where heme is synthesized. We undertook a positional cloning project to identify the causative mutation for the hemoglobin-deficit ( hbd) mouse mutant, which suffers from a microcytic, hypochromic anemia apparently due to defective iron transport in the endocytosis cycle. As shown by previous studies, reticulocyte iron accumulation in homozygous hbd/ hbd mice is deficient despite normal binding of transferrin to its receptor and normal transferrin uptake in the cell. We have identified a strong candidate gene for hbd, Sec15l1, a homologue to yeast SEC15, which encodes a key protein in vesicle docking. The hbd mice have an exon deletion in Sec15l1, which is the first known mutation of a SEC gene homologue in mammals.
ISSN:0888-7543
1089-8646
DOI:10.1016/j.ygeno.2005.09.015