Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Sci Rep. 2018 Jul 31;8(1):11491. doi: 10.1038/s41598-018-28618-0.
We investigated fibroblast growth factor 12 (FGF12) as a transcript enriched in the inner ear by searching published cDNA library databases. FGF12 is a fibroblast growth factor homologous factor, a subset of the FGF superfamily. To date, its localisation and function in the inner ear have not been determined. Here, we show that FGF12 mRNA is localised in spiral ganglion neurons (SGNs) and the vestibular ganglion. We also show that FGF12 protein is localised in SGNs, the vestibular ganglion, and nerve fibres extending beneath hair cells. Moreover, we investigated FGF12 function in auditory and vestibular systems using Fgf12-knockout (FGF12-KO) mice generated with CRISPR/Cas9 technology. Our results show that the inner ear morphology of FGF12-KO mice is not significantly different compared with wild-type mice. However, FGF12-KO mice exhibited an increased hearing threshold, as measured by the auditory brainstem response, as well as deficits in rotarod and balance beam performance tests. These results suggest that FGF12 is necessary for normal auditory and equilibrium function.
我们通过搜索已发表的 cDNA 文库数据库，研究了成纤维细胞生长因子 12（FGF12）作为在内耳中富集的转录物。FGF12 是成纤维细胞生长因子同源因子，是成纤维细胞生长因子超家族的一个子集。迄今为止，其在内耳中的定位和功能尚未确定。在这里，我们表明 FGF12 mRNA 定位于螺旋神经节神经元（SGN）和前庭神经节。我们还表明 FGF12 蛋白定位于 SGN、前庭神经节和延伸到毛细胞下方的神经纤维中。此外，我们使用 CRISPR/Cas9 技术生成的 Fgf12 敲除（FGF12-KO）小鼠研究了 FGF12 在听觉和前庭系统中的功能。我们的结果表明，与野生型小鼠相比，FGF12-KO 小鼠的内耳形态没有明显差异。然而，FGF12-KO 小鼠的听觉脑干反应测量的听力阈值增加，以及在旋转棒和平衡梁性能测试中的缺陷。这些结果表明 FGF12 对于正常的听觉和平衡功能是必要的。
