四种渐进性听力损失近交系小鼠耳蜗静纤毛早期病理特征。

Characterization of the early pathology of cochlear stereocilia in four inbred mouse strains with progressive hearing loss.

机构信息

Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, Yantai, Shandong, P.R. China.

Department of Human Anatomy and Histology and Embryology, Binzhou Medical University, Yantai, Shandong, P.R. China.

出版信息

Histol Histopathol. 2019 Jul;34(7):811-820. doi: 10.14670/HH-18-086. Epub 2019 Jan 24.

DOI:10.14670/HH-18-086

PMID:30675896

Abstract

OBJECTIVE

Inbred strains of mice offer promising models for understanding the genetic basis of age-related hearing loss (AHL). NOD/LtJ, A/J, DBA/2J and C57BL/6J mice are classical models of age-related hearing loss and exhibit early onset of pathology of AHL. This study was carried out to characterize the early pathology of cochlear stereocilia in the four mouse strains with age-related hearing loss.

METHODS

The structural features of stereocilia in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice were observed by scanning electron microscopy (SEM) at age 2, 4, 6 or 8, and 10 or 12 weeks. Meanwhile, auditory-evoked brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) amplitudes of the mice were measured at various intervals (3, 4, 6, 8, 10 and 12 weeks of age).

RESULTS

The ABR thresholds in NOD/LtJ, A/J and DBA/2J mice increased with age from 3 to 12 weeks. DPOAE amplitudes in NOD/LtJ, A/J, DBA/2J mice were very low at 4 weeks and became negative at 8 weeks at f2 frequency of 17 672 Hz. In addition to the progressive hearing loss, the four mouse strains displayed early onset (at 2 weeks of age) and progressive degeneration of stereocilia in hair cells.

CONCLUSION

Early degeneration of stereocilia contributes to the functional impairment of hair cells and hearing loss in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice.

摘要

目的

近交系小鼠为研究与年龄相关的听力损失（AHL）的遗传基础提供了有前景的模型。NOD/LtJ、A/J、DBA/2J 和 C57BL/6J 小鼠是年龄相关性听力损失的经典模型，表现出 AHL 病理的早期发病。本研究旨在表征具有年龄相关性听力损失的四种小鼠品系中耳蜗静纤毛的早期病理学。

方法

通过扫描电子显微镜（SEM）观察 NOD/LtJ、A/J、DBA/2J 和 C57BL/6J 小鼠在 2、4、6 或 8 周龄以及 10 或 12 周龄时的静纤毛结构特征。同时，在不同时间点（3、4、6、8、10 和 12 周龄）测量小鼠的听觉脑干反应（ABR）和畸变产物耳声发射（DPOAE）幅度。

结果

NOD/LtJ、A/J 和 DBA/2J 小鼠的 ABR 阈值从 3 周龄到 12 周龄逐渐升高。NOD/LtJ、A/J、DBA/2J 小鼠的 DPOAE 幅度在 4 周龄时非常低，在 8 周龄时在 17672 Hz 的 f2 频率处变为负值。除了进行性听力损失外，这四种小鼠品系还表现出静纤毛的早期发病（在 2 周龄时）和进行性毛细胞变性。