한빛사논문
- 조회5,501
Abstract
Byung Yoon Choi1, Hyoung-Mi Kim2, Taku Ito3, Kyu-Yup Lee3, Xiangming Li2, Kelly Monahan3, Yaqing Wen3, Elizabeth Wilson1, Kiyoto Kurima3, Thomas L. Saunders4, Ronald S. Petralia5, Philine Wangemann2, Thomas B. Friedman1 and Andrew J. Griffith3
1Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Rockville, Maryland, USA.
2Anatomy and Physiology Department, Kansas State University, Manhattan, Kansas, USA.
3Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, NIH, Rockville, Maryland, USA.
4Transgenic Animal Model Core, University of Michigan Medical School, Ann Arbor, Michigan, USA.
5Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA.
Address correspondence to: Andrew J. Griffith, Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, NIH, 5 Research Court, Room 2B-29, Rockville, Maryland 20850-3320, USA.
Authorship note: Byung Yoon Choi, Hyoung-Mi Kim, and Taku Ito contributed equally to this work.
Mutations in human SLC26A4 are a common cause of hearing loss associated with enlarged vestibular aqueducts (EVA). SLC26A4 encodes pendrin, an anion-base exchanger expressed in inner ear epithelial cells that secretes HCO3- into endolymph. Studies of Slc26a4-null mice indicate that pendrin is essential for inner ear development, but have not revealed whether pendrin is specifically necessary for homeostasis. Slc26a4-null mice are profoundly deaf, with severe inner ear malformations and degenerative changes that do not model the less severe human phenotype. Here, we describe studies in which we generated a binary transgenic mouse line in which Slc26a4 expression could be induced with doxycycline. The transgenes were crossed onto the Slc26a4-null background so that all functional pendrin was derived from the transgenes. Varying the temporal expression of Slc26a4 revealed that E16.5 to P2 was the critical interval in which pendrin was required for acquisition of normal hearing. Lack of pendrin during this period led to endolymphatic acidification, loss of the endocochlear potential, and failure to acquire normal hearing. Doxycycline initiation at E18.5 or discontinuation at E17.5 resulted in partial hearing loss approximating the human EVA auditory phenotype. These data collectively provide mechanistic insight into hearing loss caused by SLC26A4 mutations and establish a model for further studies of EVA-associated hearing loss.
논문정보
- Research article
- 2011년 10월 (BRIC 등록일 )
- 국외 연구진
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
