Department of Otolaryngology - Head and Neck Surgery, UC San Diego Medical Center, San Diego, CA, USA.
Department of Otolaryngology - Head and Neck Surgery, UC San Diego Medical Center, San Diego, CA, USA; Saint Louis University School of Medicine, St. Louis, MO, USA.
Hear Res. 2022 Nov;425:108505. doi: 10.1016/j.heares.2022.108505. Epub 2022 Apr 9.
Hearing loss is the most common sensory deficit worldwide, with the majority of preventable injury attributed to noise-induced hearing loss (NIHL). Highly conserved cochlear genetics between humans and mice have made this animal model a high-yield candidate for better characterizing the biologic and genetic underpinnings of human NIHL. This review aims to summarize advances in understanding the genetics of noise-induced hearing loss in mouse models dating from the early 1990s. We review the genetic mechanisms underpinning NIHL as understood in the mouse model, including histopathological and phenotypic associations, molecular and cellular mechanisms of changes in cochlear structures, synaptopathy and neuropathy, and transcriptomics. We describe variations in pathophysiology of hearing loss between mouse strains, with particular emphasis on susceptibility of different strains to different mechanisms of damage after acoustic trauma, and the potential of novel targeted therapeutic approaches for NIHL based on understanding of genetic mechanisms. Finally, we review the current state of research on the cochlear transcriptome after noise exposure in the mouse and implications for translation of these findings to humans.
听力损失是全球最常见的感觉缺陷，其中大多数可预防的损伤归因于噪声性听力损失（NIHL）。人类和小鼠之间高度保守的耳蜗遗传学使得这种动物模型成为更好地描述人类 NIHL 的生物学和遗传学基础的高产量候选者。本综述旨在总结自 20 世纪 90 年代初以来，关于小鼠模型中噪声诱导听力损失遗传的研究进展。我们回顾了在小鼠模型中理解的 NIHL 的遗传机制，包括组织病理学和表型关联、耳蜗结构变化的分子和细胞机制、突触病和神经病变以及转录组学。我们描述了不同小鼠品系之间听力损失的病理生理学差异，特别强调了不同品系对不同机制损伤的敏感性，以及基于遗传机制理解的针对 NIHL 的新型靶向治疗方法的潜力。最后，我们综述了在小鼠噪声暴露后耳蜗转录组的研究现状及其对这些发现向人类转化的影响。
