分析突变小鼠的"没有表型"挑战
Virginia E Papaioannou1, Richard R Behringer2
1Department of Genetics and Development, Columbia University Medical Center, New York, New York 10032, USA vep1@columbia.edu.
Cold Spring Harbor protocols
|November 6, 2023
概括
研究小鼠的基因功能需要仔细检查微妙的表型. 本研究概述了揭示基因突变隐藏影响的方法,这些遗传突变在标准观测中可能不明显.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 分子生物学分子生物学
- 动物模型 动物模型
背景情况:
- 尽管基因突变,但同卵性突变小鼠可能看起来很正常,这使得基因功能的研究变得复杂.
- 缺乏可观测的表型可能源于技术错误,可变透率或晚发性影响.
- 了解基因功能对于破译生物过程和疾病机制至关重要.
研究的目的:
- 确定突变小鼠缺少明显表型的潜在原因.
- 为了提供一个框架来揭示通过随意检查不显而易见的神秘表型.
- 用动物模型指导研究人员验证基因功能研究.
主要方法:
- 消除基因向和基因定型程序中的技术错误.
- 考虑可变透率和与年龄相关的或晚发症的表型 (例如瘤).
- 分析基因表达模式和蛋白质产品特征.
- 针对感官,平衡和协调使用有针对性的功能测试.
- 利用遗传和环境挑战来揭示微妙的表型偏差.
主要成果:
- 这项研究提出了一种系统的方法来识别突变小鼠中非明显的表型.
- 它强调了严格的方法和多样化的测试策略的重要性.
- 这些发现表明,看似正常的突变小鼠可能存在神秘的功能缺陷.
结论:
- 在突变小鼠中明显缺乏表型并不一定表明冗余或缺乏功能.
- 系统的调查,包括功能测定和挑战范式,对于准确的基因功能评估至关重要.
- 这种方法提高了使用小鼠模型研究基因功能和人类疾病的可靠性.
相关概念视频
02:43Mouse Models of Cancer Study
5.6K
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,...
5.6K
01:16In-vitro Mutagenesis
14.0K
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.
14.0K
02:41Lethal Alleles
15.5K
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...
15.5K