Genetically modified Animals
Frequently, animal models are produced with the help of genetic engineering methods. The ad- vantage of experiments using genetically-altered (transgenic) animals is that the intervention in the animal’s genome takes place in a targeted manner and not randomly, as is the case in cross-bree- ding. In fact, singular genes can deliberately be switched off (knockout animal) or inserted (knock- in animal) into the genome of these animals. Therefore transgenic animals allow observation of the effects of genetic modifications in living organisms. Value for research
Transgenic animals are helpful and sought-after models, particularly in basic research, especially since the mapping of the human genome. Whereas researchers now know all of the human genes, they still do not know the functions of many of them. Genetically altered animals can help find the answers, because many human genes are found in mice in a similar form.
Genetically modified? or transgenic?
Genetically modified organisms are organisms whose genetic material has been altered in a tar- geted manner with the help of genetic engineering techniques. The narrower term “transgenic” animals describes organisms in which an existing gene has been switched off or in which foreign Genetically altered/modified animals
An animal in which the heritable DNA has been intentionally altered, or the progeny of such an animal(s) or of an animal with a mutation recognised as harmful. This includes animals produced by genetic modification or by induced mutagenesis, or animals created by nuclear transfer proce- dures, as well as harmful mutant lines arising from spontaneous mutations. This definition excludes animals with changes that are not heritable, such as gene therapy interventions or DNA immunisa- New methods to overcome drawbacks
Classical animal models from genetically modified animals have a number of disadvantages. Of- ten, they are not flexible, and the altered genes are active during the wrong developmental stages or in the wrong organs. This can result in incorrect conclusions drawn from the studies. Therefore sys- tems are now increasingly being used that allow an “external” control of the activity of the genes. Examples for this are the Tet systems: The altered genes can be switched on and off at a desired
point in time by introducing or withdrawing the antibiotic tetracycline. Classical knock-out mice already carry a genetically engineered genetic defect in all of their organs at the time of their birth. This can result in undesired disorders during the development of the animals. For this reason, knock- out mice are now increasingly being produced, in which the genetic defect is limited to one type of cell or one particular organ. This can be achieved with the Cre-lox system, for example.
Another method, RNA interference (RNAi), can reduce the need for genetically modified mice for
animal testing. It allows genes to be turned off in normal animals directly in the tissue. As opposed to the eight-to-twelve months required to produce a knock-out mouse strain, only a few weeks are needed to conduct an experiment using this new technique. Another advantage is that several genes can be turned off simultaneously. This is a crucial issue in research, since many diseases are not based on a single switched-off gene, but rather on several ones. Nonetheless, RNAi also has its limitations. Knock-out mice will still be necessary in the future, since the new method does not allow switching off genes completely, but by 70 per cent at best. Genetically modified Animals
Not yet a complete answer
Better knowledge is the prerequisite for better therapies. However, even genetically engineered mice do not enable scientists to answer all open questions. Many human diseases are not caused by a change in one individual gene, but rather by the interaction of several errant genes. This ma- kes the analysis of diseases more difficult. Opponents of animal testing point to the limited explanatory power of research using genetically modified animals, and it is true that transferability of data from animals to humans varies greatly from case to case. And it can take months or years and require a large number of animals before a genetically modified strain of mice is available for use. Nevertheless, transgenic animals are helpful and therefore sought-after models, particularly in basic research.


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