Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
Genes (Basel). 2021 Jul 16;12(7):1082. doi: 10.3390/genes12071082.
Connexins are gap junction components that are essential for acquiring normal hearing ability. Up to 50% of congenital, autosomal-recessive, non-syndromic deafness can be attributed to variants in , the gene that encodes connexin 26. Gene therapies modifying the expression of connexins are a feasible treatment option for some patients with genetic hearing losses. However, the expression patterns of these proteins in the human fetus are not fully understood due to ethical concerns. Recently, the common marmoset was used as a primate animal model for the human fetus. In this study, we examined the expression patterns of connexin 26 and connexin 30 in the developing cochlea of this primate. Primate-specific spatiotemporal expression changes were revealed, which suggest the existence of primate-specific control of connexin expression patterns and specific functions of these gap junction proteins. Moreover, our results indicate that treatments for connexin-related hearing loss established in rodent models may not be appropriate for human patients, underscoring the importance of testing these treatments in primate models before applying them in human clinical trials.
缝隙连接蛋白是获得正常听力能力所必需的,高达 50%的先天性常染色体隐性非综合征性耳聋可归因于编码缝隙连接蛋白 26 的 基因的变异。改变缝隙连接蛋白表达的基因治疗是一些遗传性听力损失患者可行的治疗选择。然而,由于伦理问题,这些蛋白质在人类胎儿中的表达模式尚不完全清楚。最近,普通狨猴被用作人类胎儿的灵长类动物模型。在这项研究中,我们研究了连接蛋白 26 和连接蛋白 30 在灵长类动物耳蜗发育中的表达模式。揭示了灵长类动物特有的连接蛋白表达模式的时空表达变化,这表明连接蛋白表达模式存在灵长类动物特异性控制和这些缝隙连接蛋白的特定功能。此外,我们的研究结果表明,在啮齿动物模型中建立的与连接蛋白相关的听力损失治疗方法可能不适合人类患者,这强调了在将这些治疗方法应用于人类临床试验之前,在灵长类动物模型中进行测试的重要性。