Hearing impairment in murine model of Down syndrome.
Hearing impairment in murine model of Down syndrome.
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DOI：
10.3389/fgene.2022.936128
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发表时间：
2022
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
听力障碍是唐氏综合症（DS）的一个主要特征，但其临床表现可归因于多种因素。小鼠模型可以提供关于 DS 听力损失的各种原因的机制见解。为了研究在没有钙粘蛋白 23 突变的情况下 DS 听力损失的机制，我们将 DS 小鼠 Dp(16)1Yey 与听力正常的 CBA/J 小鼠回交，并评估其听觉功能。野生型 (WT) 和 DS 小鼠在 3 个月大时的体重相似，但在 9 个月大时，WT 比 DS 小鼠重 30%。失真产物耳声发射 (DPOAE) 是一种受传导性听力损失负面影响的感觉外毛细胞 (OHC) 功能测试，在 DS 小鼠中，所有频率的幅度和灵敏度均降低。 DS 小鼠的中耳间隙表现正常，没有感染证据。 DS 颞骨的 MicroCT 结构成像显示鼓膜直径、卵圆窗和中耳间隙较小，骨性耳囊局部增厚，但中耳小骨未见明显异常。耳蜗和前庭感觉上皮的组织学分析显示耳蜗和前庭毛细胞的密度正常；然而，DS 小鼠的耳蜗基底膜比 WT 小鼠短约 0.6 毫米，因此 WT 小鼠的毛细胞总数比 DS 小鼠多。在 DS 小鼠中，听觉脑干反应 (ABR) 的早期和晚期峰值（反映了耳蜗听觉神经随后脑干神经中枢的神经反应）幅度降低，并且所有频率的 ABR 阈值均升高到类似程度，这与传导性听力损伤一致。在相同强度下比较时，DS 小鼠的 ABR 波形峰值潜伏期比 WT 小鼠更长；然而，当以高于阈值的相同强度比较数据以补偿传导性听力损失时，延迟延迟消失了。未来的研究使用宽带鼓室导抗测试和吸光度以及中耳的详细组织学分析可以阐明 DS 小鼠传导性听力损伤的性质。
Hearing impairment is a cardinal feature of Down syndrome (DS), but its clinical manifestations have been attributed to multiple factors. Murine models could provide mechanistic insights on various causes of hearing loss in DS. To investigate mechanisms of hearing loss in DS in the absence of the cadherin 23 mutation, we backcrossed our DS mice, Dp(16)1Yey, onto normal-hearing CBA/J mice and evaluated their auditory function. Body weights of wild type (WT) and DS mice were similar at 3-months of age, but at 9-months, WT weighed 30% more than DS mice. Distortion product otoacoustic emissions (DPOAE), a test of sensory outer hair cell (OHC) function negatively impacted by conductive hearing loss, were reduced in amplitude and sensitivity across all frequencies in DS mice. The middle ear space in DS mice appeared normal with no evidence of infection. MicroCT structural imaging of DS temporal bones revealed a smaller tympanic membrane diameter, oval window, and middle ear space and localized thickening of the bony otic capsule, but no gross abnormalities of the middle ear ossicles. Histological analysis of the cochlear and vestibular sensory epithelium revealed a normal density of cochlear and vestibular hair cells; however, the cochlear basal membrane was approximately 0.6 mm shorter in DS than WT mice so that the total number of hair cells was greater in WT than DS mice. In DS mice, the early and late peaks in the auditory brainstem response (ABR), reflecting neural responses from the cochlear auditory nerve followed by subsequent neural centers in the brainstem, were reduced in amplitude and ABR thresholds were elevated to a similar degree across all frequencies, consistent with a conductive hearing impairment. The latency of the peaks in the ABR waveform were longer in DS than WT mice when compared at the same intensity; however, the latency delays disappeared when the data were compared at the same intensity above thresholds to compensate for the conductive hearing loss. Future studies using wideband tympanometry and absorbance together with detailed histological analysis of the middle ear could illuminate the nature of the conductive hearing impairment in DS mice.
影响因子：
2.5
作者：
Bhutta, Mahmood F.;Cheeseman, Michael T.;Herault, Yann;Yu, Yuejin E.;Brown, Steve D. M.
通讯作者：
Brown, Steve D. M.
唐氏综合症小鼠模型中的中耳炎。
DOI：
10.1111/j.1365-2613.2009.00677.x
发表时间：
2009-10
影响因子：
3
作者：
Han F;Yu H;Zhang J;Tian C;Schmidt C;Nava C;Davisson MT;Zheng QY
通讯作者：
Zheng QY