Auditory function in the Tc1 mouse model of down syndrome suggests a limited region of human chromosome 21 involved in otitis media.
Auditory function in the Tc1 mouse model of down syndrome suggests a limited region of human chromosome 21 involved in otitis media.
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DOI：
10.1371/journal.pone.0031433
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Marcotti W
中科院分区：
文献类型：
--
作者：
Kuhn S;Ingham N;Pearson S;Gribble SM;Clayton S;Steel KP;Marcotti W
唐氏综合症是最常见的先天性疾病之一，导致人类广泛的健康问题，包括频繁的中耳炎。除了全套小鼠染色体外，Tc1小鼠还携带人类21号染色体（Hsa21）的重要部分，并与患有21号染色体三体性唐氏综合征的人类中观察到的许多表型相同。然而，目前尚不清楚Tc1小鼠是否表现出听力表型，因此可能是了解唐氏综合征中常见的听力损失的良好模型。在这项研究中，我们进行了结构和功能评估的听力在Tc1小鼠。与同窝对照组相比，Tc1小鼠的听觉脑干反应（ABR）测量结果显示正常阈值，ABR波形潜伏期和振幅与对照组相当。Tc1和对照小鼠的中耳和内耳的大体解剖结构也相似。耳蜗感觉感受器（内毛细胞和外毛细胞）的生理特性进行了研究，使用单细胞膜片钳记录从急性解剖耳蜗。成人Tc1 IHC表现出正常的静息膜电位，并表示所有的控制毛细胞的K+电流特性。然而，大电导（BK）Ca2+激活的K+电流（IK，f）的大小，这使得准确的声音编码所必需的快速电压响应，增加了Tc1 IHC。两种基因型的OHCs的所有生理特性都无法区分。Tc1小鼠中正常的功能性听力和中耳和内耳的大体结构解剖与在显示中耳炎的唐氏综合征Ts65Dn模型中观察到的相反。在Ts65Dn中为三体而在Tc1中为二体的基因在额外的拷贝活跃时可能易患中耳炎。
Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21) in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR) measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs) were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K+ currents characteristic of control hair cells. However, the size of the large conductance (BK) Ca2+ activated K+ current (I K,f), which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active.
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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
DOI：
10.1523/jneurosci.2430-09.2009
发表时间：
2009-11-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Quina LA;Wang S;Ng L;Turner EE
通讯作者：
Turner EE
影响因子：
3.5
作者：
PALLANCK, L;GANETZKY, B
通讯作者：
GANETZKY, B
DOI：
10.1073/pnas.1016646108
发表时间：
2011-02-08
影响因子：
11.1
作者：
Kuhn, Stephanie;Johnson, Stuart L.;Marcotti, Walter
通讯作者：
Marcotti, Walter
影响因子：
10.8
作者：
Dunlevy, Louisa;Bennett, Mike;Mohun, Timothy
通讯作者：
Mohun, Timothy