Ito Taku, Watanabe Hiroki, Honda Keiji, Fujikawa Taro, Kitamura Ken, Tsutsumi Takeshi
Department of Otorhinolaryngology, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Otorhinolaryngology, Chigasaki Chuo Hospital, Kanagawa, Japan.
Front Mol Neurosci. 2024 Apr 29;17:1384764. doi: 10.3389/fnmol.2024.1384764. eCollection 2024.
Inner ear malformations are predominantly attributed to developmental arrest during the embryonic stage of membranous labyrinth development. Due to the inherent difficulty in clinically assessing the status of the membranous labyrinth, these malformations are diagnosed with radiographic imaging, based on the morphological characteristics of the bony labyrinth. While extensive research has elucidated the intricacies of membranous labyrinth development in mouse models, comprehensive investigations into the developmental trajectory of the bony labyrinth, especially about its calcification process, have been notably lacking. One of the most prominent types of inner ear malformations is known as incomplete partition (IP), characterized by nearly normal external cochlear appearance but pronounced irregularities in the morphology of the modiolus and inter-scalar septa. IP type II (IP-II), also known as Mondini dysplasia, is generally accompanied by an enlargement of the vestibular aqueduct and is primarily attributed to mutations in the gene. In the case of IP-II, the modiolus and inter-scalar septa of the cochlear apex are underdeveloped or missing, resulting in the manifestation of a cystic structure on radiographic imaging. In this overview, we not only explore the normal development of the bony labyrinth in mice but also present our observations on otolith mineralization. Furthermore, we investigated the specifics of bony labyrinth and otolith mineralization in -deficient mice, which served as an animal model for IP-II. We ensured that these findings promise to provide valuable insights for the establishment of therapeutic interventions, optimal timing, targeted sites, and preventive measures when considering the management of this condition.
内耳畸形主要归因于膜迷路发育胚胎阶段的发育停滞。由于临床上评估膜迷路状态存在固有困难，这些畸形是根据骨迷路的形态特征通过影像学检查来诊断的。虽然广泛的研究已经阐明了小鼠模型中膜迷路发育的复杂性，但对骨迷路发育轨迹，尤其是其钙化过程的全面研究明显不足。内耳畸形最突出的类型之一是不完全分隔（IP），其特征是耳蜗外观几乎正常，但蜗轴和蜗管间隔形态明显不规则。II型不完全分隔（IP-II），也称为Mondini发育异常，通常伴有前庭导水管扩大，主要归因于 基因的突变。在IP-II病例中，耳蜗顶部的蜗轴和蜗管间隔发育不全或缺失，导致影像学检查显示出囊性结构。在本综述中，我们不仅探讨了小鼠骨迷路的正常发育，还展示了我们对耳石矿化的观察结果。此外，我们研究了作为IP-II动物模型的 缺陷小鼠骨迷路和耳石矿化的具体情况。我们确信这些发现有望为在考虑这种疾病的治疗时确定治疗干预措施、最佳时机、靶向部位和预防措施提供有价值的见解。
