Genetics transgenic models

Animal models of disease play a critical role in the drug discovery process and are important in the lead candidate selection process as well. Categories of animal disease models include spontaneous disease, induced models (e.g., chemically, immunologically), xenograft models, infection models, and genetically modified models (e.g., transgenic knockouts (KOs) or knock-ins (KIs), humanized animals (e.g., expressing the human protein or receptor). The sub-... 

Price DL, Tanzi RE, Borchelt DR, Sisodia SS (1998) Alzheimer s disease Genetic studies and transgenic models. Annu Rev Genet 32 461-493. 

X. L. Xu, J. M. Olson, and L. P. Zhao, A regression-based method to identify differentially expressed genes in microarray time course studies and its application in an inducible Huntington s disease transgenic model. Hum Mol Genet 11(17) 1977-1985 (2002). 

Short- and medium-term assays in transgenic models as a basis to provide essential information about the predisposing factors to specific genetic alterations in carcinogenesis include the rat liver foci model, the XPA—/— and the p53+/— knockout mouse models, the Tg.AC and Tg.rasH2 transgenic mouse models, and Ihe neonatal... 

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. ... 

Wells T, Carter DA (2001) Genetic engineering of neural function in transgenic rodents towards a comprehensive strategy J Neurosci Methods 108 111-130. Boy ton RJ, Altmann DM (2002) Transgenic models of autoimmune disease. Clin Exp Immunol 127 4-11. 

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