What they found
Extended characterization of Strc-/- mouse cochlea at multiple ages including late (5 months). Critical data on tectorial membrane morphology and OHC structural/survival status over time.
Key findings — OHC survival timeline
| Age | Finding |
|---|---|
| P9 | Bundle structurally and functionally NORMAL |
| P10 | First morphological anomalies in some OHCs |
| P14 | Stereocilia still connected by tip links |
| P15 | Tip links begin disappearing |
| P60 | ”Almost all OHC stereocilia fully disconnected from each other” |
| 5 months | BASAL region: “only rare OHC hair bundles, all with scarce and shortened stereocilia” |
| 5 months | APICAL region: “OHC loss NOT increased compared to control mice” |
Critical distinction: basal (high-freq) OHCs degrade faster than apical (low-freq). At 5 months: apical OHCs largely preserved, basal OHCs significantly damaged.
Key findings — Tectorial membrane
TM imprints ABSENT throughout development and adulthood in Strc-/- mice:
“Stereocilia imprints on the lower surface of the tectorial membrane were not observed in Strc-/- mice”
This means: without STRC, the TM-OHC attachment crowns never form — not that they form and then degrade. The TM never embeds the OHC stereocilia tips.
However:
- Hensen’s stripe present and unaffected
- TM remains attached to spiral limbus normally
- TM gross structure maintained
Critical implication for Misha
Misha has PARTIAL STRC (VUS allele produces some protein). His TM likely DID form partial attachment crowns and imprints at birth. Unlike the full KO, he had some OHC-TM coupling. His question is not “did TM contact ever exist” (it probably did, partially) but “is it maintained at age 5?”
The apical vs basal gradient matters for Misha specifically:
- Left ear (milder, ~40-50 dB) → more apical involvement → better preserved OHCs
- Right ear (worse, ~50-65 dB) → more basal damage → more degradation
Links
- PubMed: https://pubmed.ncbi.nlm.nih.gov/21165971/
- PMC: https://pmc.ncbi.nlm.nih.gov/articles/PMC3375590/
- DOI: https://doi.org/10.1002/cne.22509
Connections
- STRC Stereocilia Bundle Mechanics Model — age-progression and TM-imprint absence; apical OHCs better preserved
- Adult Treatment Window STRC — bundle degeneration timeline supports neonatal intervention urgency
Numbers that matter (2026-04-23 audit)
Connector geometry — NOT reported in this paper. Verpy 2011 is a localization/developmental study only. No TEM connector counts, no HTC spacing measurements, no stiffness data.
- The paper confirms HTC (“horizontal top connectors”) are absent in Strc-/- and fail to form (not degraded) throughout development.
- “Resolution of immunogold labeling not sufficient to enable precise localization of stereocilin within the bands of top connectors.”
- Source for HTC_PER_STEREOCILIUM = 6 is NOT Verpy 2011. No count data here.
- No SPR/BLI, no stiffness numbers.
Verdict: Cannot validate any of the four target model parameters from this paper.