Program in Audiology and Communication Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Assoc Res Otolaryngol. 2010 Dec;11(4):605-23. doi: 10.1007/s10162-010-0228-1. Epub 2010 Aug 13.
Two inbred mouse strains, CBA/J and CBA/CaJ, have been used nearly interchangeably as 'good hearing' standards for research in hearing and deafness. We recently reported, however, that these two strains diverge after 1 year of age, such that CBA/CaJ mice show more rapid elevation of compound action potential (CAP) thresholds at high frequencies (Ohlemiller, Brain Res. 1277: 70-83, 2009). One contributor is progressive decline in endocochlear potential (EP) that appears only in CBA/CaJ. Here, we explore the cellular bases of threshold and EP disparities in old CBA/J and CBA/CaJ mice. Among the major findings, both strains exhibit a characteristic age (∼18 months in CBA/J and 24 months in CBA/CaJ) when females overtake males in sensitivity decline. Strain differences in progression of hearing loss are not due to greater hair cell loss in CBA/CaJ, but instead appear to reflect greater neuronal loss, plus more pronounced changes in the lateral wall, leading to EP decline. While both male and female CBA/CaJ show these pathologies, they are more pronounced in females. A novel feature that differed sharply by strain was moderate loss of outer sulcus cells (or 'root' cells) in spiral ligament of the upper basal turn in old CBA/CaJ mice, giving rise to deep indentations and void spaces in the ligament. We conclude that CBA/CaJ mice differ both quantitatively and qualitatively from CBA/J in age-related cochlear pathology, and model different types of presbycusis.
两种近交系小鼠品系,CBA/J 和 CBA/CaJ,几乎可以互换地用作听力和耳聋研究的“正常听力”标准。然而,我们最近报道称,这两个品系在 1 岁后出现分歧,以至于 CBA/CaJ 小鼠在高频时复合动作电位(CAP)阈值升高更快(Ohlemiller,Brain Res. 1277:70-83,2009)。一个原因是内淋巴电位(EP)的进行性下降,这种下降只出现在 CBA/CaJ 中。在这里,我们探讨了老年 CBA/J 和 CBA/CaJ 小鼠阈值和 EP 差异的细胞基础。在主要发现中,两种品系都表现出一个特征性的年龄(在 CBA/J 中约为 18 个月,在 CBA/CaJ 中约为 24 个月),此时雌性对敏感性下降的敏感性超过雄性。在听力损失进展方面的品系差异不是由于 CBA/CaJ 中毛细胞丢失更多,而是似乎反映了神经元丢失更多,加上外侧壁变化更明显,导致 EP 下降。虽然雄性和雌性 CBA/CaJ 都表现出这些病理变化,但在雌性中更为明显。一个明显不同的新特征是老年 CBA/CaJ 小鼠上基底转上外嵴细胞(或“根”细胞)中度丢失,导致韧带中出现深凹陷和空洞。我们得出结论,CBA/CaJ 小鼠在与年龄相关的耳蜗病理学方面与 CBA/J 既有数量上的差异,也有质量上的差异,并可模拟不同类型的老年性聋。