Résumé
A genetically modified mouse or genetically engineered mouse model (GEMM) is a mouse (Mus musculus) that has had its genome altered through the use of genetic engineering techniques. Genetically modified mice are commonly used for research or as animal models of human diseases, and are also used for research on genes. Together with patient-derived xenografts (PDXs), GEMMs are the most common in vivo models in cancer research. Both approaches are considered complementary and may be used to recapitulate different aspects of disease. GEMMs are also of great interest for drug development, as they facilitate target validation and the study of response, resistance, toxicity and pharmacodynamics. In 1974 Beatrice Mintz and Rudolf Jaenisch created the first genetically modified animal by inserting a DNA virus into an early-stage mouse embryo and showing that the inserted genes were present in every cell. However, the mice did not pass the transgene to their offspring, and the impact and applicability of this experiment were, therefore, limited. In 1981 the laboratories of Frank Ruddle from Yale University, Frank Costantini and Elizabeth Lacy from Oxford, and Ralph L. Brinster and Richard Palmiter in collaboration from the University of Pennsylvania and the University of Washington injected purified DNA into a single-cell mouse embryo utilizing techniques developed by Brinster in the 1960s and 1970s, showing transmission of the genetic material to subsequent generations for the first time. During the 1980s, Palmiter and Brinster developed and led the field of transgenesis, refining methods of germline modification and using these techniques to elucidate the activity and function of genes in a way not possible before their unique approach. There are two basic technical approaches to produce genetically modified mice. The first involves pronuclear injection, a technique developed and refined by Ralph L. Brinster in the 1960s and 1970s, into a single cell of the mouse embryo, where it will randomly integrate into the mouse genome.
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Concepts associés (4)
Oncomouse
The OncoMouse or Harvard mouse is a type of laboratory mouse (Mus musculus) that has been genetically modified using modifications designed by Philip Leder and Timothy A Stewart of Harvard University to carry a specific gene called an activated oncogene (v-Ha-ras under the control of the mouse mammary tumor virus promoter). The activated oncogene significantly increases the mouse's susceptibility to cancer, and thus makes the mouse a suitable model for cancer research.
Transgène
Un transgène est la séquence isolée d'un gène, transférée d'un organisme à un autre, lors de la mise en œuvre de la transgenèse. Cette modification peut altérer le comportement génétique de l'organisme (p. ex. production d'une nouvelle protéine). En agronomie, on parle de gène d’intérêt permettant de faire exprimer à un organisme un caractère choisi ; par exemple, on peut chercher à rendre une plante résistante à un antibiotique ou à augmenter sa teneur en vitamines.
Souris de laboratoire
thumb|upright=1.2|Souris blanches (variété albinos souvent utilisée par les laboratoires). L'expression « souris de laboratoire » désigne un rongeur sentient utilisé dans le cadre de recherches scientifiques ou de tests biologiques, par exemple allergologiques ou cancérologiques. Les laboratoires utilisent également l’expression « modèle murin ». Les souris communes (Mus musculus) ont été et continuent à être beaucoup utilisées comme organismes modèles en biologie, par exemple en génétique, en embryologie, en oncologie, en pharmacologie ou en toxicologie.
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