title: Methionine Sulfoxide Reductase B3-Targeted In Utero Gene Therapy Rescues Hearing Function in a Mouse Model of Congenital Sensorineural Hearing Loss.
abstract: OBJECTIVE
  Methionine sulfoxide reductase B3 (MsrB3), which stereospecifically repairs methionine-R-sulfoxide, is an important Msr protein that is associated with auditory function in mammals. MsrB3 deficiency leads to profound congenital hearing loss due to the degeneration of stereociliary bundles and the apoptotic death of cochlear hair cells. In this study, we investigated a fundamental treatment strategy in an MsrB3 deficiency mouse model and confirmed the biological significance of MsrB3 in the inner ear using MsrB3 knockout (MsrB3(-/-)) mice.
  
  
  RESULTS
  We delivered a recombinant adeno-associated virus encoding the MsrB3 gene directly into the otocyst at embryonic day 12.5 using a transuterine approach. We observed hearing recovery in the treated ears of MsrB3(-/-) mice at postnatal day 28, and we confirmed MsrB3 mRNA and protein expression in cochlear extracts. Additionally, we demonstrated that the morphology of the stereociliary bundles in the rescued ears of MsrB3(-/-) mice was similar to those in MsrB3(+/+) mice.
  
  
  METHODS
  To our knowledge, this is the first study to demonstrate functional and morphological rescue of the hair cells of the inner ear in the MsrB3 deficiency mouse model of congenital genetic sensorineural hearing loss using an in utero, virus-mediated gene therapy approach.
  
  
  CONCLUSIONS
  Our results provide insight into the role of MsrB3 in hearing function and bring us one step closer to hearing restoration as a fundamental therapy.
authors.affiliation: 1 Department of Biology, College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.|2 School of Life Sciences, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Min-A
authors.initials: MA
authors.lastname: Kim
authors.affiliation: 1 Department of Biology, College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: 1 Department of Biology, College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.|2 School of Life Sciences, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Bae
authors.affiliation: 1 Department of Biology, College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.|2 School of Life Sciences, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Byeonghyeon
authors.initials: B
authors.lastname: Lee
authors.affiliation: 1 Department of Biology, College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.|2 School of Life Sciences, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University , Daegu, Republic of Korea.|3 Division of Life Sciences, Korea Polar Research Institute (KOPRI) , Incheon, Republic of Korea.
authors.forename: Se-Kyung
authors.initials: SK
authors.lastname: Oh
authors.affiliation: 4 Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF) , Daegu, Republic of Korea.
authors.forename: Tae-Jun
authors.initials: TJ
authors.lastname: Kwon
authors.affiliation: 5 School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Zae-Young
authors.initials: ZY
authors.lastname: Ryoo
authors.affiliation: 6 Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine , Daegu, Republic of Korea.
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: 7 Department of Electronic Engineering, College of IT Engineering, Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Cho
authors.affiliation: 1 Department of Biology, College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.|2 School of Life Sciences, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Un-Kyung
authors.initials: UK
authors.lastname: Kim
authors.affiliation: 8 Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Kyu-Yup
authors.initials: KY
authors.lastname: Lee
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D051150:Methionine Sulfoxide Reductases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D014599:Uterus / Q000378:metabolism*
chemical_list: D051150:Methionine Sulfoxide Reductases; C000588563:methionine sulfoxide reductase B3, mouse