鼠标Tert基因的人性化将端粒重置为人类的长度
De Cheng1, Fan Zhang1, Kenneth I Porter1
1Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA 99202, USA.
Research square
|January 23, 2024
概括
研究人员用人性化的端粒设计了小鼠,创造了研究人类衰老和癌症的新模型. 这些小鼠表现出缩短的端粒,模仿人类的衰老,并在炎症期间显示结肠细胞更新减少.
科学领域:
- 遗传学和基因组学 在
- 衰老研究研究 衰老研究
- 分子生物学分子生物学
背景情况:
- 端粒缩短是人类衰老的生物标志物,与成人组织中端粒酶表达受限有关.
- 现有的小鼠模型对研究人类端粒生物学有局限性,原因是端粒较长和端粒酶活性广泛.
研究的目的:
- 为研究衰老和疾病设计具有人性化端粒调节的小鼠模型.
- 研究人性化端粒长度和调节对小鼠生理学和疾病反应的影响.
主要方法:
- 通过将非编码序列替换为人类对应物,设计了一种具有人性化的mTert基因 (hmTert) 的小鼠菌株.
- 调节hmTert基因以模仿成人组织中的人类TERT基因表达模式.
- 评估了基因工程小鼠的端粒长度,细胞稳态,以及对诱导性大肠炎的反应.
主要成果:
- hmTert基因成功地挽救了mTert-Knockout小鼠中的端粒功能障碍.
- 工程小鼠 (Tert) 与野生型小鼠 (50 kb) 相比,实现了类似人类的端粒长度 (10-12 kb).
- 尽管端粒缩短,Tert小鼠保持正常的平衡,但在结肠炎期间显示出减少的结肠细胞增殖.
结论:
- 在小鼠中,Tert基因在遗传上决定了端粒恒温.
- 具有人性化的端粒稳态的工程小鼠为衰老和癌症研究提供了有价值的模型.
- 这种模型可以帮助探索关于人类衰老和瘤发生的基本问题.
相关概念视频
02:15Replicative Cell Senescence
3.6K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.6K
01:16In-vitro Mutagenesis
13.9K
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.
13.9K
02:43Mouse Models of Cancer Study
5.5K
Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
5.5K