title: Iron metabolism mutant hbd mice have a deletion in Sec15l1, which has homology to a yeast gene for vesicle docking.
abstract: 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.
authors.affiliation: Department of Medical Research, Children's Mercy Hospitals and Clinics, and Department of Pediatrics-Genetics, University of Missouri at Kansas City School of Medicine, Kansas City, MO 64108, USA. rwhite@cmh.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: White
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Boydston
authors.forename: Terri R
authors.initials: TR
authors.lastname: Brookshier
authors.forename: Steven G
authors.initials: SG
authors.lastname: McNulty
authors.forename: Ndona N
authors.initials: NN
authors.lastname: Nsumu
authors.forename: Brandon P
authors.initials: BP
authors.lastname: Brewer
authors.forename: Krista
authors.initials: K
authors.lastname: Blackmore
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004705:Endocytosis / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D015870:Gene Expression; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C506790:Sec15 protein, mouse; D007501:Iron