Calcium oxalate stone formation in the inner ear as a result of an Slc26a4 mutation

J Biol Chem. 2010 Jul 9;285(28):21724-35. doi: 10.1074/jbc.M110.120188. Epub 2010 May 4.

Abstract

Calcium oxalate stone formation occurs under pathological conditions and accounts for more than 80% of all types of kidney stones. In the current study, we show for the first time that calcium oxalate stones are formed in the mouse inner ear of a genetic model for hearing loss and vestibular dysfunction in humans. The vestibular system within the inner ear is dependent on extracellular tiny calcium carbonate minerals for proper function. Thousands of these biominerals, known as otoconia, are associated with the utricle and saccule sensory maculae and are vital for mechanical stimulation of the sensory hair cells. We show that a missense mutation within the Slc26a4 gene abolishes the transport activity of its encoded protein, pendrin. As a consequence, dramatic changes in mineral composition, size, and shape occur within the utricle and saccule in a differential manner. Although abnormal giant carbonate minerals reside in the utricle at all ages, in the saccule, a gradual change in mineral composition leads to a formation of calcium oxalate in adult mice. By combining imaging and spectroscopy tools, we determined the profile of mineral composition and morphology at different time points. We propose a novel mechanism for the accumulation and aggregation of oxalate crystals in the inner ear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anion Transport Proteins / metabolism
  • Calcium Oxalate / chemistry*
  • Cochlea / pathology
  • Deafness / genetics
  • Ear, Inner / pathology
  • Extracellular Matrix / metabolism
  • Hair Cells, Auditory / metabolism
  • Humans
  • Membrane Transport Proteins / genetics*
  • Mice
  • Microscopy, Electron, Scanning / methods
  • Molecular Sequence Data
  • Mutation, Missense*
  • Rats
  • Sequence Homology, Amino Acid
  • Spectroscopy, Fourier Transform Infrared
  • Spectrum Analysis, Raman / methods
  • Sulfate Transporters

Substances

  • Anion Transport Proteins
  • Membrane Transport Proteins
  • SLC26A4 protein, human
  • Slc26a4 protein, mouse
  • Sulfate Transporters
  • Calcium Oxalate