Molecular Therapy
Volume 4, Issue 6, December 2001, Pages 575-585
Journal home page for Molecular Therapy

Article
The Functional and Structural Outcome of Inner Ear Gene Transfer via the Vestibular and Cochlear Fluids in Mice

https://doi.org/10.1006/mthe.2001.0490Get rights and content
Under a Creative Commons license
open archive

Abstract

Mice present an ideal model for inner ear gene therapy because their genome is being rapidly sequenced, their generation time is relatively short, and they serve as a valuable model for human hereditary inner ear disease. However, the small size of the mouse inner ear poses a particular challenge for surgical procedures. We have developed a new approach for viral inoculation into the mature mouse inner ear, using a replication-deficient adenovirus expressing the bacterial gene lacZ. We administered the virus through the posterior semicircular canal (canalostomy) and into the cochlea (cochleostomy). Both approaches caused lacZ to be expressed in cells lining the perilymphatic space. One canalostomy case showed gene expression in sensory cells of the crista ampullaris, whereas the cochleostomy group showed gene expression in the sensory cells in the organ of Corti and saccule. Functional tests after the surgery showed that the canalostomy preserved hearing, whereas the cochleostomy did not. Any vestibular function transiently lost after the canalostomy was recovered. Our findings indicate that inoculation of adenovirus vectors into the mouse inner ear through the semicircular canal has the potential to efficiently introduce transgenes to the vestibular system and the cochlea without compromising hearing.

Key Words

mouse
gene transfer
adenovirus
lacZ
semicircular canal
cochleostomy
ABR
vestibular function

Cited by (0)