Influence of genetic background on genetically engineered mouse phenotypes.
Influence of genetic background on genetically engineered mouse phenotypes.
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DOI：
10.1007/978-1-59745-471-1_23
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Doetschman, Thomas
中科院分区：
文献类型：
--
作者：
Doetschman, Thomas
小鼠遗传学的历史表明，放置基因靶向等位基因的遗传背景会导致基因工程小鼠(GEM)表型的相当大的差异。这种变异可以表现为完全不同的表型，表现为表型外显性的变化，也可以表现为表型的不同表现。在这一章中，我们提供了基因靶向文献中的例子，展示了每一种类型的表型变异。我们讨论了修饰基因如何影响带有突变基因的小鼠的表型，并给出了修饰基因位点识别的例子。我们还回顾了减少实验动物之间以及它们和它们的对照之间的基因多态和侧翼基因差异的方法。此外，我们还讨论了在混合遗传背景下对基因敲除小鼠进行首次分析的优点和缺点。我们的结论是，混合背景提供了可能的菌株依赖表型的最快预览。最后，我们回顾了最近通过产生新的近交系来改善遗传多样性的方法，这些近交系包含了小鼠物种中更广泛的等位基因。
The history of mouse genetics, which involves the study of strain-dependent phenotype variability, makes it clear that the genetic background onto which a gene-targeted allele is placed can cause considerable variation in genetically engineered mouse (GEM) phenotype. This variation can present itself as completely different phenotypes, as variations in penetrance of phenotype, or as variable expressivity of phenotype. In this chapter we provide examples from gene-targeting literature showing each of these types of phenotype variation. We discuss ways in which modifier genes can affect the phenotype of a mouse with a mutant gene, and we give examples of modifier locus identification. We also review approaches to minimize gene polymorphism and flanking gene differences between experimental animals, and between them and their controls. In addition, we discuss the advantages and disadvantages of performing the first analysis of a knockout mouse on a mixed genetic background. We conclude that a mixed background provides the quickest preview of possible strain-dependent phenotypes. Finally, we review recent approaches to improving genetic diversity by generating new inbred strains that encompass a broader range of alleles within the mouse species.
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影响因子：
30.8
作者：
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通讯作者：
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通讯作者：
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通讯作者：
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