胚胎致命表型鉴定用于识别与出生缺陷相关的候选基因
Bing Yan1, Baoming Gong1, Yufang Zheng1
1State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200441, China.
International journal of molecular sciences
|August 29, 2024
概括
这项研究分析了致命的突变小鼠菌株,揭示了心脏和神经系统发育的缺陷,并确定了与人类疾病的联系. 这些发现提供了对先天性出生缺陷和肥胖病因学的见解.
科学领域:
- 发育生物学 发展生物学
- 遗传学 是一个遗传学.
- 人类疾病病理学病理学
背景情况:
- 先天性出生缺陷是婴儿死亡率和残疾的主要原因.
- 了解这些缺陷的遗传机制对于临床干预至关重要.
研究的目的:
- 通过随机突变发生产生的致命突变菌株的胚胎和周产期表型的分析.
- 识别与先天性缺陷有关的基因和途径.
- 探索突变与人类疾病和肥胖之间的潜在联系.
主要方法:
- 产生和表型55致命突变菌株携带PiggyBac (PB) 转位子插件.
- 利用了基因本体学 (GO) 和基因和基因组的京都百科全书 (KEGG) 路径分析.
- 检查了粗体形态,发育迟缓和特定器官系统缺陷 (大脑,心脏,血管系统).
主要成果:
- 53个菌株被证实是胚胎或围产期致命的.
- 常见的表型包括异常体型,发育迟缓,大脑缺陷和心血管异常.
- 已知有12个突变的位置与人类疾病有关.
- 包括TGF-β信号基因Smad2在内的八个菌株的异构体显示出改变的体重和组成.
结论:
- 对心脏和神经系统发育至关重要的基因的突变,以及Notch/Wnt信号传递,有助于先天性缺陷.
- 这项研究为了解哺乳动物胚胎发育和先天性出生缺陷病理学提供了宝贵的资源.
- 确定了Smad2异性和改变的能量代谢之间的联系,这表明对肥胖病因的含义.
相关概念视频
02:41Lethal Alleles
15.4K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.4K
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
01:07Teratogenicity
2.4K
The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
2.4K