TAILIEUCHUNG - Chapter 062. Principles of Human Genetics (Part 10)

Transgenic Mice as Models of Genetic Disease Several organisms have been studied extensively as genetic models, including Mus musculus (mouse), Drosophila melanogaster (fruit fly), Caenorhabditis elegans (nematode), Saccharomyces cerevisiae (baker's yeast), and Escherichia coli (colonic bacterium). The ability to use these evolutionarily distant organisms as genetic models that are relevant to human physiology reflects a surprising conservation of genetic pathways and gene function. Transgenic mouse models have been particularly valuable, because many human and mouse genes exhibit similar structure and function, and because manipulation of the mouse genome is relatively straightforward compared to those of other mammalian species. . | Chapter 062. Principles of Human Genetics Part 10 Transgenic Mice as Models of Genetic Disease Several organisms have been studied extensively as genetic models including Mus musculus mouse Drosophila melanogaster fruit fly Caenorhabditis elegans nematode Saccharomyces cerevisiae baker s yeast and Escherichia coli colonic bacterium . The ability to use these evolutionarily distant organisms as genetic models that are relevant to human physiology reflects a surprising conservation of genetic pathways and gene function. Transgenic mouse models have been particularly valuable because many human and mouse genes exhibit similar structure and function and because manipulation of the mouse genome is relatively straightforward compared to those of other mammalian species. Transgenic strategies in mice can be divided into two main approaches 1 expression of a gene by random insertion into the genome and 2 deletion or targeted mutagenesis of a gene by homologous recombination with the native endogenous gene knock-out knock-in Fig. 62-6 Table 62-3 . Transgenic mice are generated by pronuclear injection of foreign DNA into fertilized mouse oocytes and subsequent transfer into the oviduct of pseudopregnant foster mothers. Figure 62-6 Transgenic mouse models. Left. Transgenic mice are generated by pronuclear injection of foreign DNA into fertilized mouse oocytes and subsequent transfer into the oviduct of pseudopregnant foster mothers. Right. For targeted mutagenesis gene knock-out knock-in embryonic stem ES cells are transfected with the targeted mutagenized transgene. The transgene undergoes homologous recombination with the wild-type gene. After selection positive ES cells are introduced into blastocysts and implanted into foster mothers. Chimeric mice can be identified based on the mixed coat color of the offspring. Heterozygous mice are bred to obtain mice homozygous for the mutant allele. Table 62-3 Genetically Modified Animals Commonly Used Description Technical Principle

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