구.추천논문
- 조회3,995
Abstract
Tae-Jun Kwon1,†, Hyun-Ju Cho1,†, Un-Kyung Kim1,†, Eujin Lee6, Se-Kyung Oh1, Jinwoong Bok7,8, Yong Chul Bae2, Jun-Koo Yi3,9, Jang Woo Lee4, Zae-Young Ryoo3, Sang Heun Lee5, Kyu-Yup Lee5,* and Hwa-Young Kim6,*
1Department of Biology, College of Natural Sciences,
2Department of Oral Anatomy and Neurobiology, School of Dentistry,
3School of Life Science and Biotechnology, College of Natural Sciences,
4Graduate School of Electrical Engineering and Computer Science and
5Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
6Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu, Republic of Korea,
7Department of Anatomy and
8BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
9Gyeongsangbuk-do Livestock Research Institute, Yeoungju, Republic of Korea
*To whom correspondence should be addressed at: Department of Otorhinolaryngology, School of Medicine, Kyungpook National University, Daegu 700-721, Republic of Korea. Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, 170 Hyeonchungno, Namgu, Daegu 705-717, Republic of Korea.
Abstract
Methionine sulfoxide reductase B3 (MsrB3) is a protein repair enzyme that specifically reduces methionine-R-sulfoxide to methionine. A recent genetic study showed that the MSRB3 gene is associated with autosomal recessive hearing loss in human deafness DFNB74. However, the precise role of MSRB3 in the auditory system and the pathogenesis of hearing loss have not yet been determined. This work is the first to generate MsrB3 knockout mice to elucidate the possible pathological mechanisms of hearing loss observed in DFNB74 patients. We found that homozygous MsrB3-/- mice were profoundly deaf and had largely unaffected vestibular function, whereas heterozygous MsrB3+/- mice exhibited normal hearing similar to that of wild-type mice. The MsrB3 protein is expressed in the sensory epithelia of the cochlear and vestibular tissues, beginning at E15.5 and E13.5, respectively. Interestingly, MsrB3 is densely localized at the base of stereocilia on the apical surface of auditory hair cells. MsrB3 deficiency led to progressive degeneration of stereociliary bundles starting at P8, followed by a loss of hair cells, resulting in profound deafness in MsrB3-/- mice. The hair cell loss appeared to be mediated by apoptotic cell death, which was measured using TUNEL and caspase 3 immunocytochemistry. Taken together, our data suggest that MsrB3 plays an essential role in maintaining the integrity of hair cells, possibly explaining the pathogenesis of DFNB74 deafness in humans caused by MSRB3 deficiency.
논문정보
- Research article
- 2013년 11월 (BRIC 등록일 )
- 국내 연구진
- 의약학 > 유전 및 유전체의학
- 구・추천논문
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