development of gene therapy for auditory and vestibular disorders-gene delivery into the cochlear

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12557142
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 展開研究
• 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): 2000 – 2001
• Keywords: adeno virus vector / HVJ-liposome / sensorineural hearing loss / gene delivery / klotho gene / 血管条 / コルチ器 / ラセン神経節細胞 / 呼吸上皮

Research Abstract

Auditory function of klotho gene knock out (kl/kl) mouse was evaluated by measuring of ABR and EP of kl/kl mouse was significantly deteriorated compared with those of wild mouse, suggesting that kl/kl mouse has sensorineural hearing loss. RT-PCR and immunohistochemical analysis indicated that there was no expression of klotho mRNA and protein in the cochlea. The results suggest that klotho protein secreted from other tissues must reach to the cochlea via blood circulation and exert its physiological action there as a humoral factor essential for normal auditory function. Intra-cochlear and intra-cutaneous gene delivery of normal klotho gene with adeno virus vector (AVV) was found to be able to rescue completely the auditory function of kl/kl mouse. Gene delivery into the cochlea with HVJ-lipose was also found to be effective.