Iizuka Takashi, Kamiya Kazusaku, Gotoh Satoru, Sugitani Yoshinobu, Suzuki Masaaki, Noda Tetsuo, Minowa Osamu, Ikeda Katsuhisa
Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan.
Department of Cell Biology, Japanese Foundation for Cancer Research, Cancer Institute, Tokyo 135-8550, Japan.
Hum Mol Genet. 2015 Jul 1;24(13):3651-61. doi: 10.1093/hmg/ddv109. Epub 2015 Mar 23.
Hearing loss is the most widespread sensory disorder, with an incidence of congenital genetic deafness of 1 in 1600 children. For many ethnic populations, the most prevalent form of genetic deafness is caused by recessive mutations in the gene gap junction protein, beta 2, 26 kDa (GJB2), which is also known as connexin 26 (Cx26). Despite this knowledge, existing treatment strategies do not completely recover speech perception. Here we used a gene delivery system to rescue hearing in a mouse model of Gjb2 deletion. Mice lacking Cx26 are characterized by profound deafness from birth and improper development of cochlear cells. Cochlear delivery of Gjb2 using an adeno-associated virus significantly improved the auditory responses and development of the cochlear structure. Using gene replacement to restore hearing in a new mouse model of Gjb2-related deafness may lead to the development of therapies for human hereditary deafness.
听力损失是最普遍的感觉障碍，先天性遗传性耳聋的发病率为每1600名儿童中有1例。对于许多种族群体来说，最常见的遗传性耳聋形式是由缝隙连接蛋白β2（26 kDa，GJB2）基因中的隐性突变引起的，该蛋白也被称为连接蛋白26（Cx26）。尽管有这些认识，但现有的治疗策略并不能完全恢复言语感知。在这里，我们使用基因递送系统在Gjb2缺失的小鼠模型中挽救听力。缺乏Cx26的小鼠的特征是从出生起就严重耳聋，并且耳蜗细胞发育不当。使用腺相关病毒将Gjb2递送至耳蜗可显著改善听觉反应和耳蜗结构的发育。在新的Gjb2相关耳聋小鼠模型中使用基因替代来恢复听力可能会导致人类遗传性耳聋治疗方法的发展。
