人类突变的MYOT和CRYAB基因在斑马鱼中引起肌病性表型
Elena Cannone1, Valeria Guglielmi2, Giulia Marchetto2
1Department of Molecular and Translational Medicine, Zebrafish Facility, University of Brescia, 25123 Brescia, Italy.
International journal of molecular sciences
|July 29, 2023
概括
肌林和alphaB-crystallin中的突变会导致肌纤维肌肉病变 (MFM). 带有这些突变的斑马鱼模型发展肌肉缺陷,为疾病机制和潜在的药物标提供了洞察力.
科学领域:
- 肌肉生物学 肌肉生物学
- 遗传学 遗传学 是一个
- 神经肌肉疾病 神经肌肉疾病
背景情况:
- 肌纤维肌病 (MFMs) 是一种遗传性神经肌肉疾病,其特征是肌肉纤维分解和蛋白质聚合物.
- 编码结构蛋白或伴侣蛋白的基因突变导致MFMs,但确切的致病机制尚不清楚.
研究的目的:
- 调查肌肉素和αB-晶体素在MFM病变发生过程中的作用.
- 为研究MFM和确定治疗点建立斑马鱼模型.
主要方法:
- 注射了野生型或突变人类MYOT和CRYAB基因的斑马鱼胚胎.
- 评估鱼类的生存,运动行为,肌肉结构和蛋白质聚合.
- 使用转基因斑马鱼来建模MFM.
主要成果:
- 转基因斑马鱼表现出形态和肌肉缺陷,特别是突变基因过度表达.
- 突变基因表达导致蛋白质聚合物的形成,模仿人类的MFM.
- 斑马鱼模型显示了与人类MFM一致的肌病性表型.
结论:
- 肌素和alphaB-crystallin中的致病突变会损害斑马鱼的骨肌肉结构和功能.
- 斑马鱼作为一种有价值的非哺乳动物模型,用于剖析MFM的病原性.
- 这种模型可以帮助发现MFM治疗的可用药物点.
相关概念视频
Mutations
Overview
Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Background and Environment Affect Phenotype
Although the genetic makeup of an organism plays a major role in determining the phenotype, there are also several environmental factors, such as temperature, oxygen availability, presence of mutagens, that can alter an organism’s phenotype.
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Formation of Muscle Fibers from Myoblasts
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life


