相关实验视频

Updated: Jun 14, 2025

Direct Reprogramming of Human Fibroblasts into Myoblasts to Investigate Therapies for Neuromuscular Disorders

Direct Reprogramming of Human Fibroblasts into Myoblasts to Investigate Therapies for Neuromuscular Disorders

Published on: April 3, 2021

在DFNB4小鼠模型中,通过CRISPR/Cas9介导的外显子跳转来恢复过早的翻译终止

Chun-Ying Huang^1,2, Yi-Hsiu Tsai³, Yi-Fen Cheng¹

¹Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.

|September 4, 2024

概括

在SLC26A4听力损失的小鼠模型中,CRISPR/Cas9基因编辑成功地恢复了pendrin表达和前庭功能. 然而,听力功能没有得到改善,这表明需要新的策略.

科学领域:

遗传学遗传学是一个
耳鼻喉科耳鼻喉科耳鼻喉科
分子生物学分子生物学

背景情况:

在SLC26A4中发生的突变,特别是东亚人中常见的c.919-2 A>G拼接位突变,导致内耳功能障碍和听力损失.
这种功能障碍会破坏电解质平衡,导致Pendred综合征和DFNB4.4等疾病.

研究的目的:

开发和评估一种CRISPR/Cas9介导的外子跳转策略,用于治疗与SLC26A4相关的听力损失.
创建一个Slc26a4^{∆E8+E9/∆E8+E9}小鼠模型来评估这种基因编辑方法的有效性.

主要方法:

使用CRISPR/Cas9基因编辑来诱导Slc26a4基因中的外跳转.
分析了由此产生的小鼠模型的内耳中的丁林表达.
在Slc26a4^{∆E8+E9/∆E8+E9}小鼠中评估了静脉和听觉功能.

主要成果:

在Slc26a4^{∆E8+E9/∆E8+E9}小鼠的内耳中表现出恢复的pendrin表达.
在基因编辑的小鼠中,静脉功能是正常的,与具有c.919-2 A>G突变的模型不同.
尽管分子纠正和前庭功能正常,听觉功能仍然受损,耳毛细胞损失和听力值升高.

结论:

在SLC26A4突变的小鼠模型中,CRISPR/Cas9介导的外因子跳转可以纠正pendrin表达并恢复前体功能.
仅靠这种方法就不足以恢复听力功能,这凸显了SLC26A4相关听力损失的复杂性.
替代基因编辑策略是必要的,以有效地治疗由SLC26A4 c.919-2 A>G突变引起的听力损失.

更多相关视频

CRISPR/Cas9 Editing of the C. elegans rbm-3.2 Gene using the dpy-10 Co-CRISPR Screening Marker and Assembled Ribonucleoprotein Complexes.

CRISPR/Cas9 Editing of the C. elegans rbm-3.2 Gene using the dpy-10 Co-CRISPR Screening Marker and Assembled Ribonucleoprotein Complexes.

Published on: December 11, 2020

Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein

Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein

Published on: March 16, 2022

相关概念视频

CRISPR

CRISPR

Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...

In-vitro Mutagenesis

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.