Verpy 2008 — Stereocilin-Deficient Mice Reveal Cochlear Waveform Distortions
Citation: Verpy E, Leibovici M, Michalski N, Goodyear RJ, Houdon C, Weil D, Richardson GP, Petit C. (2008). “Stereocilin-deficient mice reveal the origin of cochlear waveform distortions.” Nature, 456, 255–258.
DOI: 10.1038/nature07380
PMC: PMC3338146
File: ~/BookLibrary/incoming/Verpy_2008_Stereocilin-deficient-mice-cochlear-waveform_Nature.pdf
Key Findings
- First characterization of STRC knockout mouse model
- Stereocilin forms horizontal top connectors between stereocilia of OHCs and attachment crowns connecting tallest row stereocilia to tectorial membrane (TM)
- Without STRC: OHC stereocilia still deflect with sound but waveform is distorted — loss of fine mechanical tuning
- DPOAEs (Distortion Product Otoacoustic Emissions) absent in STRC-null mice → this is the functional readout for STRC function
- ABR thresholds elevated ~40-50 dB → moderate-to-severe hearing loss (matches DFNB16 human phenotype)
Mechanistic Insight
STRC is not required for basic hair cell survival but is critical for:
- Precise mechanical coupling of OHC stereocilia bundle
- Electromotility feedback from OHC to TM (cochlear amplification)
- DPOAE generation — clinical diagnostic marker for STRC function
Relevance to Misha
- Defines the molecular mechanism of Misha’s hearing loss
- DPOAEs absent = gold standard diagnostic for DFNB16
- Recovery of DPOAEs = key endpoint in gene therapy trials
- OHC viability confirmed even in adult STRC-null mice → therapy window not time-limited by OHC death (unlike GJB2 where cells die)
Connections
- Misha [applies]
- STRC Gene Therapy Landscape 2026 [source]
- Iranfar 2026 — Dual AAV STRC [see-also]
- DFNB16 Hearing Loss [source]
- Omichi_2020_AAV_hair_cell_transduction [see-also]