Genetically modified mouse

A genetically modified mouse (Mus musculus) is a mouse 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.

In 1974 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, Frank Costantini and Elizabeth Lacy from Oxford, and Ralph 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 early eighties, 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 never possible before their unique approach.

There are two basic technical approaches to produce genetically modified mice. The first involves pronuclear injection into a single cell of the mouse embryo, where it will randomly integrate into the mouse genome. This method creates a transgenic mouse and is used to insert new genetic information into the mouse genome or to over-express endogenous genes. The second approach, pioneered by Oliver Smithies and Mario Capecchi, involves modifying embryonic stem cells with a DNA construct containing DNA sequences homologous to the target gene. Embryonic stem cells that recombine with the genomic DNA are selected for and they are then injected into the mice . This method is used to manipulate a single gene, in most cases "knocking out" the target gene, although more subtle genetic manipulation can occur (e.g. only changing single nucleotides).

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