Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, China.
Neural Plast. 2021 Apr 17;2021:5585394. doi: 10.1155/2021/5585394. eCollection 2021.
mice exhibit severer defects in the development of the cochlea and develop deafness, while the underlying mechanisms responsible for these effects remain unclear. Our study was to investigate the potential mechanism linking deficiency to hearing loss.
RNA sequencing was applied to analyze the differential gene expression of the stria vascularis (SV) from wildtype and mice. GO and KEGG pathway analysis were performed. Quantitative RT-PCR was applied to validate the expression of candidate genes affected by . ELISA and immunofluorescence technique were used to detect the homocysteine (Hcy) level in serum, brain, and SV, respectively.
183 upregulated genes and 63 downregulated genes were identified in the SV associated with depletion. Transcriptomic profiling revealed that deficiency significantly affected the expression of genes associated with cell adhesion, transmembrane transport, and the biogenesis of multicellular organisms. The SV from mice exhibited a higher expression of mRNAs, as well as altered homocysteine (Hcy) metabolism.
The altered expression of results in a dramatic change in multiple biochemical reactions and a disruption of nutrient homeostasis in the endolymph which may contribute to hearing loss of knockout mouse.
与野生型相比, 基因敲除小鼠耳蜗发育严重缺陷并致聋,但导致这些影响的潜在机制尚不清楚。本研究旨在探讨 基因缺失与听力损失之间的潜在联系。
采用 RNA 测序分析野生型和 基因敲除小鼠血管纹的差异基因表达。进行 GO 和 KEGG 通路分析。采用定量 RT-PCR 验证受 影响的候选基因的表达。采用 ELISA 和免疫荧光技术分别检测血清、脑组织和血管纹中的同型半胱氨酸(Hcy)水平。
在与 基因耗竭相关的血管纹中,鉴定出 183 个上调基因和 63 个下调基因。转录组谱分析表明, 基因缺失显著影响与细胞黏附、跨膜转运和多细胞生物发生相关的基因表达。 基因敲除小鼠的血管纹中 mRNA 的表达增加,同型半胱氨酸(Hcy)代谢也发生改变。
基因的异常表达导致多种生化反应的剧烈变化和内淋巴中营养物质稳态的破坏,这可能导致 基因敲除小鼠的听力损失。