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

Genomics. 2005 Dec;86(6):668-73. doi: 10.1016/j.ygeno.2005.09.015. Epub 2005 Nov 11.

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.

Publication types

  • Comparative Study

MeSH terms

  • Anemia, Iron-Deficiency / genetics*
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Cloning, Molecular
  • DNA Mutational Analysis
  • Endocytosis / genetics*
  • Exons / genetics*
  • Gene Expression*
  • Iron / metabolism*
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Sequence Deletion / genetics*
  • Transport Vesicles / metabolism

Substances

  • Membrane Proteins
  • Sec15 protein, mouse
  • Iron