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Hearing research
Jan, 2012;283 (1-2): 80-8.

Genetic background effects on age-related hearing loss associated with Cdh23 variants in mice.

Kelly L Kane, Chantal M Longo-Guess, Leona H Gagnon, Dalian Ding, Richard J Salvi, Kenneth R Johnson
Author Information
  1. Kelly L Kane: The Jackson Laboratory, Bar Harbor, 600 Main Street, ME 04609, USA.
PMID: 22138310 DOI: 10.1016/j.heares.2011.11.007

Abstract

Inbred strain variants of the Cdh23 gene have been shown to influence the onset and progression of age-related hearing loss (AHL) in mice. In linkage backcrosses, the recessive Cdh23 allele (ahl) of the C57BL/6J strain, when homozygous, confers increased susceptibility to AHL, while the dominant allele (Ahl+) of the CBA/CaJ strain confers resistance. To determine the isolated effects of these alleles on different strain backgrounds, we produced the reciprocal congenic strains B6.CBACa-Cdh23(Ahl)(+) and CBACa.B6-Cdh23(ahl) and tested 15-30 mice from each for hearing loss progression. ABR thresholds for 8 kHz, 16 kHz, and 32 kHz pure-tone stimuli were measured at 3, 6, 9, 12, 15 and 18 months of age and compared with age-matched mice of the C57BL/6J and CBA/CaJ parental strains. Mice of the C57BL/6N strain, which is the source of embryonic stem cells for the large International Knockout Mouse Consortium, were also tested for comparisons with C57BL/6J mice. Mice of the C57BL/6J and C57BL/6N strains exhibited identical hearing loss profiles: their 32 kHz ABR thresholds were significantly higher than those of CBA/CaJ and congenic strain mice by 6 months of age, and their 16 kHz thresholds were significantly higher by 12 months. Thresholds of the CBA/CaJ, the B6.CBACa-Cdh23(Ahl)(+), and the CBACa.B6-Cdh23(ahl) strain mice differed little from one another and only slightly increased throughout the 18-month test period. Hearing loss, which corresponded well with cochlear hair cell loss, was most profound in the C57BL/6J and C57BL/6NJ strains. These results indicate that the CBA/CaJ-derived Cdh23(Ahl)(+) allele dramatically lessens hearing loss and hair cell death in an otherwise C57BL/6J genetic background, but that the C57BL/6J-derived Cdh23(ahl) allele has little effect on hearing loss in an otherwise CBA/CaJ background. We conclude that although Cdh23(ahl) homozygosity is necessary, it is not by itself sufficient to account for the accelerated hearing loss of C57BL/6J mice.

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Grants

  1. R01 DC005827/NIDCD NIH HHS
  2. P30 CA034196/NCI NIH HHS
  3. DC005827/NIDCD NIH HHS
  4. CA34196/NCI NIH HHS
  5. R01 DC005827-08/NIDCD NIH HHS

MeSH Term

Acoustic Stimulation
Age Factors
Aging
Animals
Audiometry, Pure-Tone
Auditory Threshold
Cadherins
Cochlea
Disease Models, Animal
Evoked Potentials, Auditory, Brain Stem
Female
Genetic Predisposition to Disease
Hair Cells, Auditory
Male
Mice
Mice, Congenic
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
Phenotype
Polymorphism, Single Nucleotide
Presbycusis
Species Specificity

Chemicals

Cadherins
Cdh23 protein, mouse
Comparative Study Journal Article Research Support, N.I.H., Extramural

Word Cloud

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