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Updated: Mar 24, 2026
Data Acquisition and Analysis In Brainstem Evoked Response Audiometry In Mice
Published on: May 10, 2019
QTL Mapping of Endocochlear Potential Differences between C57BL/6J and BALB/cJ mice
Kevin K Ohlemiller1, Anna L Kiener2, Patricia M Gagnon3
1Department of Otolaryngology, Central Institute for the Deaf at Washington University School of Medicine, Fay and Carl Simons Center for Hearing and Deafness, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO, 63110, USA. kohlemiller@wustl.edu.
Genetic mapping identified key regions and candidate genes influencing endocochlear potential (EP) variation and noise-induced reduction in mice. This research sheds light on genetic factors contributing to hearing loss.
Area of Science:
- Genetics and Auditory Physiology
- Molecular Biology and Neuroscience
Background:
- Endocochlear potential (EP) differences exist between C57BL/6J (B6) and BALB/cJ (BALB) mice, with BALB mice exhibiting lower EP and marginal cell density.
- BALB mice show susceptibility to EP reduction after noise exposure, potentially modeling age-related hearing loss (presbycusis) and contributing to noise-induced threshold shifts.
- Previous studies established strain-specific EP responses to noise, highlighting the need to identify underlying genetic factors.
Purpose of the Study:
- To identify genes and alleles responsible for natural EP variation and noise-related EP reduction in BALB mice.
- To map quantitative trait loci (QTLs) associated with EP and cochlear marginal cell density using a B6 x BALB recombinant inbred (RI) mouse model.
Main Methods:
- Quantitative trait loci (QTL) mapping was performed using 12 B6 x BALB RI strains.
- EP and strial marginal cell density were measured in naive and noise-exposed (broadband noise, 110 dB SPL, 2 h) mice.
- Strain distribution patterns were analyzed to generate QTL maps for EP and marginal cell density.
Main Results:
- A significant QTL for marginal cell density (Maced) was identified on chromosome 12, overlapping a weak EP variation QTL, implicating marginal cell density in natural EP variation.
- Candidate genes for Maced include Foxg1, Foxa1, Akap6, Nkx2-1, and Pax9.
- QTL mapping in noise-exposed RI mice revealed four suggestive regions for EP changes, with two overlapping previously identified noise-related EP reduction QTLs (Nirep) on chromosomes 5 and 18. The Nirep interval on chromosome 18 was narrowed to a ~10-Mb region.
Conclusions:
- This study provides the first exploration of natural gene variants modulating the endocochlear potential (EP).
- The identified QTLs and candidate genes offer insights into the genetic basis of EP regulation and susceptibility to hearing loss.
- Orthologs of these genes may play a role in human hearing loss originating in the cochlear lateral wall.
