A new spontaneous mutation in the mouse protocadherin 15 gene

Q. Y. Zheng, H. Yu, J. L. Washington, L. B. Kisley, Y. S. Kikkawa, K. S. Pawlowski, C. G. Wright, K. N. Alagramam

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

We have characterized a new allele of the protocadherin 15 gene (designatedPcdh15av-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 Pcdh15av-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 Pcdh15av-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.

Original languageEnglish (US)
Pages (from-to)110-120
Number of pages11
JournalHearing Research
Volume219
Issue number1-2
DOIs
StatePublished - Sep 2006

Fingerprint

Stereocilia
Alleles
Outer Auditory Hair Cells
Inner Auditory Hair Cells
Mutation
Auditory Hair Cells
Genes
Phenotype
Acoustic Stimulation
Cochlea
Cadherins

Keywords

  • Cochlear hair cells
  • Deafness
  • Mouse
  • Pcdh15

ASJC Scopus subject areas

  • Sensory Systems

Cite this

Zheng, Q. Y., Yu, H., Washington, J. L., Kisley, L. B., Kikkawa, Y. S., Pawlowski, K. S., ... Alagramam, K. N. (2006). A new spontaneous mutation in the mouse protocadherin 15 gene. Hearing Research, 219(1-2), 110-120. https://doi.org/10.1016/j.heares.2006.06.010

A new spontaneous mutation in the mouse protocadherin 15 gene. / Zheng, Q. Y.; Yu, H.; Washington, J. L.; Kisley, L. B.; Kikkawa, Y. S.; Pawlowski, K. S.; Wright, C. G.; Alagramam, K. N.

In: Hearing Research, Vol. 219, No. 1-2, 09.2006, p. 110-120.

Research output: Contribution to journalArticle

Zheng, QY, Yu, H, Washington, JL, Kisley, LB, Kikkawa, YS, Pawlowski, KS, Wright, CG & Alagramam, KN 2006, 'A new spontaneous mutation in the mouse protocadherin 15 gene', Hearing Research, vol. 219, no. 1-2, pp. 110-120. https://doi.org/10.1016/j.heares.2006.06.010
Zheng QY, Yu H, Washington JL, Kisley LB, Kikkawa YS, Pawlowski KS et al. A new spontaneous mutation in the mouse protocadherin 15 gene. Hearing Research. 2006 Sep;219(1-2):110-120. https://doi.org/10.1016/j.heares.2006.06.010
Zheng, Q. Y. ; Yu, H. ; Washington, J. L. ; Kisley, L. B. ; Kikkawa, Y. S. ; Pawlowski, K. S. ; Wright, C. G. ; Alagramam, K. N. / A new spontaneous mutation in the mouse protocadherin 15 gene. In: Hearing Research. 2006 ; Vol. 219, No. 1-2. pp. 110-120.
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