Attanasio Chiara, Palladino Antonio, Giaquinto Daniela, Scavizzi Ferdinando, Raspa Marcello, Peres Chiara, Anastasio Camilla, Scocco Paola, Lucini Carla, de Girolamo Paolo, D'Angelo Livia, De Felice Elena
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, Italy.
Department of Agricultural Sciences, University of Naples Federico II, Naples, Italy.
Aging Cell. 2025 Jan;24(1):e14362. doi: 10.1111/acel.14362. Epub 2024 Oct 31.
Morphological mouse phenotyping plays a pivotal role in the translational setting and even more in the area of auditory research, where mouse is a central model organism due to the evolutionary genetic relationship and morpho-functional analogies with the human auditory system. However, some results obtained in murine models cannot be translated to humans due to the inadequate description of experimental conditions underlying poor reproducibility. We approach the characterization of the aging process of the mouse cochlea in animals up to 18 months of age belonging to two of the most used outbred (CD1) and inbred (C57BL/6N) strains. Striving to reduce any environmental variable we performed our study compliantly to the ARRIVE guidelines. We integrated instrumental data (auditory brainstem response test), with morphological analyses to correlate functional discrepancies to morphological changes and track the differences in the evolution of sensorineural hearing loss in the two strains. We featured the localization of Gipc3, Myosin VIIa, and TMC1 in hair cells of the Corti organ as well as NF 200 and the density of type I neuron in the spiral ganglion. We outlined age-related hearing loss (ARHL) in both strains, and a clear drop in the selected marker localization. However, in CD1 we detected a different trend allowing the identification of potential strain-specific mechanisms, namely an increase in myosin VIIa in 6 months aging mice in comparison to 2 months old animals. Our findings represent an asset to investigate the strain-dependent physiological trigger of ARHL providing new insights in the translational area.
形态学小鼠表型分析在转化研究中起着关键作用,在听觉研究领域更是如此,由于小鼠与人类听觉系统存在进化遗传关系和形态功能类比,它是核心模式生物。然而,由于对实验条件描述不足导致重现性差,一些在小鼠模型中获得的结果无法转化到人类身上。我们对属于两种最常用的远交(CD1)和近交(C57BL/6N)品系、年龄达18个月的动物的小鼠耳蜗衰老过程进行了表征。为努力减少任何环境变量,我们按照ARRIVE指南开展了研究。我们将仪器数据(听觉脑干反应测试)与形态学分析相结合,以将功能差异与形态变化相关联,并追踪两种品系中感音神经性听力损失演变的差异。我们对Gipc3、肌球蛋白VIIa和TMC1在柯蒂氏器毛细胞中的定位以及NF 200和螺旋神经节中I型神经元的密度进行了特征描述。我们概述了两种品系中的年龄相关性听力损失(ARHL)以及所选标志物定位的明显下降。然而,在CD1中我们检测到一种不同趋势,这使得能够识别潜在的品系特异性机制,即与2个月龄动物相比,6个月龄衰老小鼠中肌球蛋白VIIa增加。我们的研究结果为研究ARHL的品系依赖性生理触发因素提供了宝贵资源,在转化研究领域提供了新的见解。