Chawla Amita, McCullagh Elizabeth A
Department of Integrative Biology, Oklahoma State University, Stillwater, OK, United States.
Front Integr Neurosci. 2022 Jan 17;15:803483. doi: 10.3389/fnint.2021.803483. eCollection 2021.
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.
感觉超敏反应，尤其是在听觉系统中，是脆性X综合征（FXS）的常见症状，FXS是最常见的单基因形式的智力残疾。然而，将小鼠模型的不同遗传背景品系的表型联系起来一直是一项挑战，这可能是药物研究转化到人类情况时出现一些问题的潜在原因。本研究首次在FXS常用的小鼠背景品系模型C57BL/6J中，对听觉脑干反应（ABR）进行了表征，ABR是一种微创的早期听觉处理生理读数，在人类中也会使用。我们测量了耳廓和头部的形态特征，并使用ABR测量了听力范围，以及与野生型小鼠相比，半合子雄性、纯合子雌性和杂合子雌性的单耳和双耳听觉反应。与先前的研究一致，我们发现不同基因型或性别之间的形态学参数没有差异。性别或基因型之间的听力范围没有显著差异，然而，雄性FXS小鼠有高频听力损失的趋势。相比之下，纯合FXS的雌性小鼠单耳ABR的波IV振幅降低，而雄性在振幅方面没有差异，并且ABR波形的潜伏期在不同性别和基因型之间没有变化。最后，与野生型雄性相比，患有FXS的雄性在双耳时间差为0时双耳相互作用成分（BIC）的潜伏期增加。这些发现通过在不同遗传背景品系中增加更多信息，进一步阐明了FXS中的听觉脑干处理过程，从而有助于更好地理解共同的表型。
