Genetic mouse models for bone studies--strengths and limitations.
Genetic mouse models for bone studies--strengths and limitations.
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DOI：
10.1016/j.bone.2011.08.021
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发表时间：
2011-12
期刊：
影响因子：
4.1
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Elefteriou F;Yang X
小鼠已经成为骨研究的首选模型系统，因为它们在遗传和病理生理学上与人类相似：繁殖期相对较短，导致维护成本相对较低，并且可以获得整个小鼠基因组序列信息。三十年前，第一个在小鼠红细胞中表达兔β-珠蛋白的转基因小鼠品系的成功，标志着开始使用基因工程小鼠作为研究人类疾病的模型系统。不久之后，培养的多能胚胎干细胞的发展为小鼠的基因替换或基因缺失提供了可能性。这些技术对于识别与骨骼发育、生长、重塑、修复和疾病有关的新基因至关重要，但像许多其他方法一样，它们也有局限性。这篇综述将介绍允许产生转基因小鼠和全局或条件性(组织特异性和可诱导的)突变小鼠的方法。用于实现骨特异性基因缺失或过度表达的各种启动子的列表被包括在内。讨论了这些方法的局限性，并提供了与遗传小鼠模型分析相关的一般指南。
Mice have become a preferred model system for bone research because of their genetic and pathophysiological similarities to humans: a relatively short reproductive period, leading to relatively low cost of maintenance and the availability of the entire mouse genome sequence information. The success in producing the first transgenic mouse line that expressed rabbit β-globin protein in mouse erythrocytes three decades ago marked the beginning of the use of genetically engineered mice as model system to study human diseases. Soon afterward the development of cultured pluripotent embryonic stem cells provided the possibility of gene replacement or gene deletion in mice. These technologies have been critical to identify new genes involved in bone development, growth, remodeling, repair, and diseases, but like many other approaches, they have limitations. This review will introduce the approaches that allow the generation of transgenic mice and global or conditional (tissue-specific and inducible) mutant mice. A list of the various promoters used to achieve bone-specific gene deletion or overexpression is included. The limitations of these approaches are discussed, and general guidelines related to the analysis of genetic mouse models are provided.