Role of the Mouse Ank Gene in Control of Tissue Calcification and Arthritis

Science. 2000 Jul 14;289(5477):265-70. doi: 10.1126/science.289.5477.265.

Abstract

Mutation at the mouse progressive ankylosis (ank) locus causes a generalized, progressive form of arthritis accompanied by mineral deposition, formation of bony outgrowths, and joint destruction. Here, we show that the ank locus encodes a multipass transmembrane protein (ANK) that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells. A highly conserved gene is present in humans and other vertebrates. These results identify ANK-mediated control of pyrophosphate levels as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arthritis / genetics*
  • Arthritis / metabolism
  • Arthritis / pathology
  • Base Sequence
  • Biological Transport
  • COS Cells
  • Calcinosis / genetics*
  • Chromosome Mapping
  • Cloning, Molecular
  • DNA
  • Diphosphates / metabolism*
  • Durapatite / metabolism
  • Gene Expression
  • Genetic Complementation Test
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Phosphate Transport Proteins
  • Physical Chromosome Mapping
  • Sequence Homology, Nucleic Acid
  • Tissue Distribution

Substances

  • ANKH protein, human
  • Diphosphates
  • Membrane Proteins
  • Phosphate Transport Proteins
  • ank protein, mouse
  • DNA
  • Durapatite