Evidence mapPaperPMID 39482437Full record

ArticleCommunications biology2024

PKHD1L1 is required for stereocilia bundle maintenance, durable hearing function and resilience to noise exposure.

Olga S Strelkova, Richard T Osgood, Chunjie Tian, Xinyuan Zhang, Evan Hale, Pedro De-la-Torre, Daniel M Hathaway, Artur A Indzhykulian

Abstract read
In one paragraph

Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. ThemedRxiv : the preprint server for health sciences · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Olga S Strelkova *Department of Otolaryngology Head and Neck Surgery, Mass Eye and Ear, Harvard Medical School, Boston, MA, USA.
Richard T Osgood *Department of Otolaryngology Head and Neck Surgery, Mass Eye and Ear, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-0347-9614
Chunjie Tian *Department of Otolaryngology Head and Neck Surgery, Mass Eye and Ear, Harvard Medical School, Boston, MA, USA.
Xinyuan ZhangDepartment of Otolaryngology Head and Neck Surgery, Mass Eye and Ear, Harvard Medical School, Boston, MA, USA.
Evan HaleDepartment of Otolaryngology Head and Neck Surgery, Mass Eye and Ear, Harvard Medical School, Boston, MA, USA.
Pedro De-la-TorreDepartment of Otolaryngology Head and Neck Surgery, Mass Eye and Ear, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-2434-3345
Daniel M HathawayDepartment of Otolaryngology Head and Neck Surgery, Mass Eye and Ear, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-6186-0798
Artur A IndzhykulianDepartment of Otolaryngology Head and Neck Surgery, Mass Eye and Ear, Harvard Medical School, Boston, MA, USA. inartur@hms.harvard.edu.ORCID 0000-0002-2076-6818

Funding

TRAINING FOR SPEECH AND HEARING SCIENCEST32DC000038 · NIDCD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Gwenaelle S Geleoc · 1992 to 2026
$21.8M
Molecular Basis of Hair Cell Stereocilia Bundle MorphologyR01DC017166 · NIDCD · MASSACHUSETTS EYE AND EAR INFIRMARY · PI INDZHYKULIAN, ARTUR · 2018 to 2022
$3.5M
Development of Gene Therapy for Hereditary Deafness using Rational Protein EngineeringR01DC020190 · NIDCD · MASSACHUSETTS EYE AND EAR INFIRMARY · PI DAVID P COREY, Artur Indzhykulian · 2022 to 2026
$3.3M
NIDCD NIH HHS R01 DC017166NIDCD NIH HHS R01 DC020190NIDCD NIH HHS T32 DC000038U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD) DC000038U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD) R01DC017166U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD) R01DC020190
6 · The paper itself

Abstract

Polycystic Kidney and Hepatic Disease 1-Like 1 (PKHD1L1) is a human deafness gene, responsible for autosomal recessive deafness-124 (DFNB124). Sensory hair cells of the cochlea are essential for hearing, relying on the mechanosensitive stereocilia bundle at their apical pole for their function. PKHD1L1 is a stereocilia protein required for the formation of the developmentally transient stereocilia surface coat. In this study, we carry out an in depth characterization of PKHD1L1 expression in mice during development and adulthood, analyze hair-cell bundle morphology and hearing function in aging PKHD1L1-deficient mouse lines, and assess their susceptibility to noise damage. Our findings reveal that PKHD1L1-deficient mice display no disruption to bundle cohesion or tectorial membrane attachment-crown formation during development. However, starting from 6 weeks of age, PKHD1L1-deficient mice display missing stereocilia and disruptions to bundle coherence. Both conditional and constitutive PKHD1L1 knockout mice develop high-frequency hearing loss progressing to lower frequencies with age. Furthermore, PKHD1L1-deficient mice are susceptible to permanent hearing loss following moderate acoustic overexposure, which induces only temporary hearing threshold shifts in wild-type mice. These results suggest a role for PKHD1L1 in establishing robust sensory hair bundles during development, necessary for maintaining bundle cohesion and function in response to acoustic trauma and aging.

Indexed as

Hair Cells, AuditoryHearingReceptors, Cell SurfaceStereociliaAnimalsCochleaMaleMiceMice, Inbred C57BLMice, KnockoutNoisePkhd1l1 protein, mouseReceptors, Cell Surface

Identifiers

PMID39482437
PMCPMC11527881

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.