Model organisms are essential to study the genetic basis of human diseases. Transgenic mammalian models, especially genetic knock-out mice catalysed the progress. To continue the advancement, further sophisticated and refined models are crucially needed to study the genetic basis and manifestations of numerous human diseases. In order to enhance our genetic understanding of human diseases, this proposal is aimed to develop new tools for the generation of transgenic laboratory animal models both in mouse and rat for comparative analyses of functional genomics in different species. In the mouse stable embryonic stem cell lines enable gene-targeting technology. However, the lack of such cell lines in most mammalians has so far prevented targeted genetic modifications.
This proposal is aimed to use new tools such as nuclear replacement and gene targeting in somatic cells as a technological platform for producing new transgenic models. The primary aim is to further explore and validate the nuclear replacement system for safety and reliability as a technological platform. Our goal is also to generate the first gene targeted rat models. Relevant issues, such as the role of mitochondrial inheritance, somatic cell gene targeting and standardisation of newly generated genotypes by cryo-preservation will be addressed as well.
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