Auditory Brain Stem Responses in the C57BL/6J Fragile X Syndrome-Knockout Mouse Model.
Auditory Brain Stem Responses in the C57BL/6J Fragile X Syndrome-Knockout Mouse Model.
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DOI：
10.3389/fnint.2021.803483
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发表时间：
2021
影响因子：
3.5
通讯作者：
McCullagh EA
中科院分区：
文献类型：
--
作者：
Chawla A;McCullagh EA
感觉过敏，特别是在听觉系统，是脆性X综合征(FXS)的常见症状，FXS是最常见的单基因智力残疾形式。然而，将小鼠模型的遗传背景菌株的表型联系起来一直是一个挑战，可能会低估药物研究在人类条件下的可译性的一些问题。这项研究首次在常用的FXS小鼠背景株模型C57BL/6J中表征了听性脑干反应(ABR)，这是一种早期听觉加工的微创生理读数，也用于人类。我们测量了耳廓和头部的形态特征，并使用ABR测量了半合子雄性、纯合子雌性和杂合子雌性小鼠的听力范围以及单耳和双耳听觉反应，并与野生型小鼠进行了比较。与之前的研究一致，我们显示不同的基因类型或性别在形态参数上没有差异。雄性FXS小鼠的听力范围在性别和基因类型之间没有显著差异，但有高频听力损失的趋势。相比之下，FXS纯合子雌性小鼠的单耳ABR的IV波的波幅降低，而雄性小鼠的ABR波幅和潜伏期在性别和基因类型之间没有差异。最后，与野生型男性相比，患有FXS的男性在0耳间时差时双耳相互作用成分(BIC)的潜伏期延长。这些发现通过增加遗传背景菌株之间的更多信息，进一步阐明了FXS中的听觉脑干处理，从而允许更好地理解共同的表型。
Sensory hypersensitivity, especially in the auditory system, is a common symptom in Fragile X syndrome (FXS), the most common monogenic form of intellectual disability. However, linking phenotypes across genetic background strains of mouse models has been a challenge and could underly some of the issues with translatability of drug studies to the human condition. This study is the first to characterize the auditory brain stem response (ABR), a minimally invasive physiological readout of early auditory processing that is also used in humans, in a commonly used mouse background strain model of FXS, C57BL/6J. We measured morphological features of pinna and head and used ABR to measure the hearing range, and monaural and binaural auditory responses in hemizygous males, homozygous females, and heterozygous females compared with those in wild-type mice. Consistent with previous study, we showed no difference in morphological parameters across genotypes or sexes. There was no significant difference in hearing range between the sexes or genotypes, however there was a trend towards high frequency hearing loss in male FXS mice. In contrast, female mice with homozygous FXS had a decreased amplitude of wave IV of the monaural ABR, while there was no difference in males for amplitudes and no change in latency of ABR waveforms across sexes and genotypes. Finally, males with FXS had an increased latency of the binaural interaction component (BIC) at 0 interaural timing difference compared with that in wild-type males. These findings further clarify auditory brain stem processing in FXS by adding more information across genetic background strains allowing for a better understanding of shared phenotypes.
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