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为正常发育需要极度保存的增强剂

Diane E Dickel1, Athena R Ypsilanti2, Ramón Pla2

  • 1Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA.

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|January 24, 2018
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概括

超保存增强剂对于哺乳动物的正常发育至关重要. 删除Arx基因附近的这些序列导致了微妙的神经和生长缺陷,

关键词:
没有.大脑发育增强剂基因调节海马在体内淘汰赛神经元没有编码超级保存的

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科学领域:

  • 基因组学
  • 发育生物学
  • 神经科学

背景情况:

  • 非编码的超保守区域 (UCR) 是哺乳动物基因组中高度保守的序列.
  • 这些UCR可以作为远程作用的增强剂,调节基因表达.
  • 之前的研究显示UCR删除对生存能力没有直接影响.

研究的目的:

  • 研究超保守增强剂在正常发育中的作用.
  • 确定位于Arx基因附近的特定UCR的功能重要性.

主要方法:

  • 使用基因组编辑来创建缺少单个或组合的UCR的淘汰老鼠.
  • 专注于全基因组中最长的UCR,特别是Arx基因附近的UCR.
  • 在突变小鼠中分析了神经和生长表型.

主要成果:

  • 单个或双重UCR删除的小鼠是可活的和肥沃的.
  • 几乎所有的突变小鼠都表现出神经异常和生长缺陷.
  • 观察到神经元数量和大脑结构缺陷的重大变化.

结论:

  • 超保存增强剂对于哺乳动物的正常发育至关重要.
  • 在UCR中强烈的序列保存可能反映了在标准实验室条件下不明显的适应性缺陷.
  • 这些发现突显了UCR在发展和进化的功能意义.