The functional and structural outcome of inner ear gene transfer via the vestibular and cochlear fluids in mice.
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.
Kawamoto
K
K
Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, The University of Michigan, Ann Arbor, Michigan 48109-0506, USA.
Oh
S H
SH
Kanzaki
S
S
Brown
N
N
Raphael
Y
Y
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D003051:Cochlea / Q000502:physiology*; D004432:Ear, Middle / Q000502:physiology; D016057:Evoked Potentials, Auditory, Brain Stem; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D007763:Lac Operon / Q000235:genetics; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics; D014722:Vestibule, Labyrinth / Q000502:physiology*