A new spontaneous mutation in the mouse protocadherin 15 gene

Hear Res. 2006 Sep;219(1-2):110-20. doi: 10.1016/j.heares.2006.06.010. Epub 2006 Aug 2.

Abstract

We have characterized a new allele of the protocadherin 15 gene (designatedPcdh15(av-6J)) that arose as a spontaneous, recessive mutation in the C57BL/6J inbred strain at Jackson Laboratory. Analysis revealed an inframe deletion in Pcdh15, which is predicted to result in partial deletion of cadherin domain (domain 9) in Pcdh15. Morphologic study revealed normal to moderately defective cochlear hair cell stereocilia in Pcdh15(av-6J) mutants at postnatal day 2 (P2). Stereocilia abnormalities were consistently present at P5 and P10. Degenerative changes including loss of inner and outer hair cells were seen at P20, with severe sensory cell loss in all cochlear turns occurring by P40. The hair cell phenotype observed in the 6J allele between P0 and P20 is the least severe phenotype yet observed in Pcdh15 alleles. However, young Pcdh15(av-6J) mice are unresponsive to auditory stimulation and show circling behavior indicative of vestibular dysfunction. Since these animals show severe functional deficits but have relatively mild stereocilia defects at a young age they may provide an appropriate model to test for a direct role of Pcdh15 in mechanotransduction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cadherin Related Proteins
  • Cadherins / chemistry
  • Cadherins / genetics*
  • DNA Mutational Analysis
  • Deafness / genetics*
  • Disease Models, Animal
  • Evoked Potentials, Auditory, Brain Stem
  • Exons / genetics
  • Female
  • Hair Cells, Auditory / ultrastructure
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Scanning
  • Molecular Sequence Data
  • Mutation*
  • Phenotype
  • Protein Precursors / chemistry
  • Protein Precursors / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis

Substances

  • CDHR15 protein, mouse
  • Cadherin Related Proteins
  • Cadherins
  • Protein Precursors