PKHD1L1 is required for stereocilia bundle maintenance, durable hearing function and resilience to noise exposure.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
01 Nov 2024
01 Nov 2024
Historique:
received:
16
05
2024
accepted:
22
10
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
1
11
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39482437
doi: 10.1038/s42003-024-07121-5
pii: 10.1038/s42003-024-07121-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1423Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)
ID : R01DC020190
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)
ID : R01DC017166
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)
ID : DC000038
Informations de copyright
© 2024. The Author(s).
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