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免疫缺陷 STAT1 敲除小鼠的听觉功能分析:病毒感染模型的考虑因素。

Auditory function analysis in immunodeficient STAT1 knock-out mice: Considerations for viral infection models.

机构信息

Department of Otolaryngology, University of Texas Medical Branch, USA.

Department of Pathology, University of Texas Medical Branch, USA.

出版信息

Neurosci Lett. 2021 Jan 1;740:135427. doi: 10.1016/j.neulet.2020.135427. Epub 2020 Oct 15.

Abstract

The STAT1 knock-out (KO) mouse is a frequently used transgenic immunodeficient strain to model human viral and bacterial diseases. The Lassa fever model was established in the STAT1 KO mice mimicking phenotypes seen in human patients including deafness in survivors. This model develops hearing loss at high prevalence and is a valuable tool to investigate viral infection-induced hearing loss. However, Lassa virus is a highly contagious and regulated agent requiring the unique logistics of the biosafety level 4 posing limitations for experimental work. Therefore, we did a detailed auditory analysis of the STAT1 KO mice to assess baseline auditory function in preparation for further auditory behavioral studies. Auditory brainstem response and distortion product otoacoustic emission tests were performed on males and females of the STAT1 KO mice and was compared to 129S6/SvEv wild type (WT) mice. The male WT mice had the best auditory performance and the female WT mice had the worst hearing performance. The male and female STAT1 KO mice had similar auditory performance to each other, which was intermediate between WT males and females. We conclude that both male and female STAT1 KO mice are suitable for studying viral infection-induced hearing loss.

摘要

STAT1 敲除(KO)小鼠是一种常用于模拟人类病毒和细菌疾病的转基因免疫缺陷品系。在 STAT1 KO 小鼠中建立了拉沙热模型,模拟了人类患者的表型,包括幸存者中的耳聋。该模型以高患病率发生听力损失,是研究病毒感染引起的听力损失的有价值工具。然而,拉沙病毒是一种高度传染性和受管制的病原体,需要四级生物安全的独特物流,这对实验工作造成了限制。因此,我们对 STAT1 KO 小鼠进行了详细的听觉分析,为进一步的听觉行为研究做好了基础听觉功能的评估。我们对 STAT1 KO 小鼠的雄性和雌性进行了听觉脑干反应和畸变产物耳声发射测试,并与 129S6/SvEv 野生型(WT)小鼠进行了比较。雄性 WT 小鼠的听觉表现最佳,而雌性 WT 小鼠的听力表现最差。雄性和雌性 STAT1 KO 小鼠的听觉表现彼此相似,介于 WT 雄性和雌性之间。我们得出结论,雄性和雌性 STAT1 KO 小鼠均适合研究病毒感染引起的听力损失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e426/7708419/c0733b683bb2/nihms-1638345-f0001.jpg

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