Embryonic stem cells knockout mice

In our opinion, the model of choice to study a genetic defrciency is a knockout model. This implies that the model animal has to be a mouse, since only in murine embryonic stem cells it has been possible to efficiently create tiie desired genetic alterations while pertaining fliese cells pluripotent, a prerequisite for proper embryonic development. Thus, in contrast to transgenic model systems, which in principle can be generated in any mammalian qrecies by means of oocyte microinjection, tbe choice of animal for knockout studies is limited to the mouse. Techniques to analyse cardiovascular function are well developed for larger animal models, and some of these are now modified for the small size of the mouse heart and for the animal s rapid cardiac cycle. ... 

To create a knockout mouse, one starts with a cDNA that encodes the gene of interest. One removes a portion of the gene that renders it inactive, and replaces that portion with a gene that allows one to select out those cells that have replaced a functional copy with the newly constructed mutated version. The new construct is placed into cells termed embryonic stem (ES) cells, which have the ability to grow into viable offspring when placed into pseudopregnant mothers. 

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