title: Over-expression of X-linked inhibitor of apoptosis protein slows presbycusis in C57BL/6J mice.
abstract: Apoptosis of cochlear cells plays a significant role in age-related hearing loss or presbycusis. In this study, we evaluated whether over-expression of the anti-apoptotic protein known as X-linked Inhibitor of Apoptosis Protein (XIAP) slows the development of presbycusis. We compared the age-related hearing loss between transgenic (TG) mice that over-express human XIAP tagged with 6-Myc (Myc-XIAP) on a pure C57BL/6J genetic background with wild-type (WT) littermates by measuring auditory brainstem responses. The result showed that TG mice developed hearing loss considerably more slowly than WT littermates, primarily within the high-frequency range. The average total hair cell loss was significantly less in TG mice than WT littermates. Although levels of Myc-XIAP in the ear remained constant at 2 and 14 months, there was a marked increase in the amount of endogenous XIAP from 2 to 14 months in the cochlea, but not in the brain, in both genotypes. These results suggest that XIAP over-expression reduces age-related hearing loss and hair cell death in the cochlea.
authors.affiliation: The Affiliated Sixth People's Hospital, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, China. jian.wang@dal.ca
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Trevor
authors.initials: T
authors.lastname: Menchenton
authors.forename: Shankai
authors.initials: S
authors.lastname: Yin
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Yu
authors.forename: Manohar
authors.initials: M
authors.lastname: Bance
authors.forename: David P
authors.initials: DP
authors.lastname: Morris
authors.forename: Craig S
authors.initials: CS
authors.lastname: Moore
authors.forename: Robert G
authors.initials: RG
authors.lastname: Korneluk
authors.forename: George S
authors.initials: GS
authors.lastname: Robertson