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乙醇焦虑溶解的候选基因Ninein在C57BL/6J和DBA/2J小鼠之间表现出复杂的外子特异表达和替代拼接差异
E R Gnatowski1,2, J L Jurmain1, M G Dozmorov2,3
1Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, United States.
Frontiers in genetics
|September 26, 2024
概括
在Ninein (Nin) 基因拼接中的遗传差异影响着乙醇.
科学领域:
- 神经遗传学 神经遗传学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 乙醇的抗焦虑作用与增加的消费和酒精使用障碍 (AUD) 有关.
- 之前的研究在BXD小鼠中确定了与乙醇抗焦虑特性相关的基因位点.
- 尼宁 (Nin) 被确定为一种候选基因,影响乙醇的急性抗焦虑作用.
研究的目的:
- 调查Ninein (Nin) 替代拼接的菌株特异性是否有助于C57BL/6J (B6) 和DBA/2J (D2) 小鼠之间的乙醇焦虑解的变化.
- 分析这些拼接差异对Nin基因表达和蛋白质功能的影响.
主要方法:
- 定量逆转录酶PCR (RT-qPCR) 用于分析小鼠大脑区域 (前额叶皮质,核,杏仁体) 的Nin拼接变异.
- 深度RNA测序 (RNA-seq) 用于评估全球Nin表达,外因子利用和核内核中的替代拼接事件.
- 在D2 Nin外体中单核酸多态 (SNPs) 的生物信息分析.
主要成果:
- 在B6和D2小鼠之间确定了对Nin的显著异型特异性外因表达差异.
- 与B6小鼠相比,在D2小鼠中发现了显著更高的总Nin表达.
- 检测到八个差异化利用的外形子,包括三个新的3'末端拼接事件,仅限于D2小鼠,以及D2 Nin外形子中的有害SNP.
结论:
- 大脑中的Ninein (Nin) 基因的菌株特异替代拼接是B6和D2小鼠之间差异性乙醇焦虑解的潜在机制.
- 这些发现为乙醇对焦虑和AUD风险的影响的遗传基础提供了新的见解.
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