Gene delivery with adeno virus vector into the inner ear of deaf mouse

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671679
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Osaka University
• Principal Investigator: DOI Katsumi Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (40243224)
• Co-Investigator(Kenkyū-buntansha): TAMURA Manabu Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50273644)
• Project Period (FY): 1999 – 2000
• Keywords: adeno virus vector / gene therapy / deafness / cochlea

Research Abstract

Therapeutic manipulations of the mammalian cochlea, including cochlear gene transfer, have been studied using mouse as the experimental deaf model. With the significant developments in mouse genomics and the availability of mutant strains of mice with well-characterized hearing loss, the mouse will be preferred animal model for therapeutic manipulations. This study describes a ventral approach, instead of the routinely used postauricular approach in other rodents, for accessing the middle and inner ear of the kl/kl mouse (klotho gene knock-out mouse), and its application in cochlea gene transfer. This ventral approach enabled rapid and direct delivery of klotho gene with adeno virus vector to the klotho mouse inner ear while avoiding blood loss, facial nerve morbidity, and mortality. Transgene expression at 3 days was detected in the organ of Corti, spiral ganglion cells, spiral ligament, in a pattern similar to the previously described in the guinea pig cochlea. The successful access and delivery of klotho gene to the kl/kl mouse cochlea resulted in a rescue from hearing loss. The replication of gene expression seen in this study should promote the use of the deaf mouse in future studies investigating targeted cochlear gene therapy.