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Gene therapy for hereditary hearing loss by SLC26A4 mutations in mice reveals distinct functional roles of pendrin in normal hearing

 Min-A Kim  ;  Sung Huhn Kim  ;  Nari Ryu  ;  Ji-Hyun Ma  ;  Ye-Ri Kim  ;  Jinsei Jung  ;  Chuan-Jen Hsu  ;  Jae Young Choi  ;  Kyu-Yup Lee  ;  Philine Wangemann  ;  Jinwoong Bok  ;  Un-Kyung Kim 
 THERANOSTICS, Vol.9(24) : 7184-7199, 2019 
Journal Title
Issue Date
Enlarged vestibular aqueduct ; Gene therapy ; In-utero ; Pendred syndrome ; Recombinant adeno-associated virus ; Solute carrier family 26 member 4
Rationale: Mutations of SLC26A4 that abrogate pendrin, expressed in endolymphatic sac, cochlea and vestibule, are known to cause autosomal recessive sensorineural hearing loss with enlargement of the membranous labyrinth. This is the first study to demonstrate the feasibility of gene therapy for pendrin-related hearing loss. Methods: We used a recombinant viral vector to transfect Slc26a4 cDNA into embryonic day 12.5 otocysts of pendrin-deficient knock-out (Slc26a4∆/∆ ) and pendrin-deficient knock-in (Slc26a4tm1Dontuh/tm1Dontuh ) mice. Results: Local gene-delivery resulted in spatially and temporally limited pendrin expression, prevented enlargement, failed to restore vestibular function, but succeeded in the restoration of hearing. Restored hearing phenotypes included normal hearing as well as sudden, fluctuating, and progressive hearing loss. Conclusion: Our study illustrates the feasibility of gene therapy for pendrin-related hearing loss, suggests differences in the requirement of pendrin between the cochlea and the vestibular labyrinth, and documents that insufficient pendrin expression during late embryonal and early postnatal development of the inner ear can cause sudden, fluctuating and progressive hearing loss without obligatory enlargement of the membranous labyrinth.
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1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sung Huhn(김성헌)
Bok, Jin Woong(복진웅) ORCID logo https://orcid.org/0000-0003-1958-1872
Jung, Jinsei(정진세) ORCID logo https://orcid.org/0000-0003-1906-6969
Choi, Jae Young(최재영) ORCID logo https://orcid.org/0000-0001-9493-3458
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