Selective ablation of inner hair cells and subsequent in-situ hair cell regeneration in the neonatal mouse cochlea.
Diphtheria toxin
Inner ear
Inner hair cell
Outer hair cell
Regeneration
Spiral ganglion neuron
Journal
Hearing research
ISSN: 1878-5891
Titre abrégé: Hear Res
Pays: Netherlands
ID NLM: 7900445
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
08
10
2020
revised:
24
04
2021
accepted:
10
05
2021
pubmed:
6
6
2021
medline:
8
2
2022
entrez:
5
6
2021
Statut:
ppublish
Résumé
Loss of hair cells (HCs) accounts for most sensorineural hearing loss, and regeneration of cochlear HCs is considered as the ultimate strategy for restoring hearing. Several lines of evidence have shown that Lgr5+ progenitor cells can spontaneously regenerate new HCs after HC loss at the neonatal stage, and most of which are immature. IHCs are resistant to ototoxic drugs and noise and cannot be ablated efficiently in order to precisely investigate IHC regeneration in existing hearing injury models, and thus we generated a new transgenic mouse model by inserting diphtheria toxin receptor (DTR) under the control of the Vglut3 promoter. In this model, IHCs were selectively ablated in a dose-dependent manner after the injection of diphtheria toxin (DT) at the neonatal stage, while OHCs remained intact with normal hair bundle structures until adulthood. With this IHC-specific injury model, we observed HC regeneration from Lgr5+ progenitors after IHC ablation at the neonatal stage. Some of the newly generated HCs replaced the lost IHCs in-situ and re-build the structure of the organ of Corti through the asymmetrical mitosis of progenitor cells. While, the majority of the regenerated HCs did not survive until adulthood, and the loss of spiral ganglion neurons was observed after the IHC ablation, which led to profound hearing loss after DT injection in Vglut3
Identifiants
pubmed: 34089989
pii: S0378-5955(21)00109-X
doi: 10.1016/j.heares.2021.108275
pii:
doi:
Substances chimiques
Diphtheria Toxin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108275Informations de copyright
Copyright © 2021. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no competing interests.