Knockout transgene

Weissman C, Raeber AJ, Shmerling D, Aguzzi A, Manson JC. Knockouts, transgenics, and transplants in prion research. In Prusiner SB, ed. Prion Biology and Diseases. Vol. 38. Cold Spring Harbor, NY Cold Spring Harbor Press, 1999 273-305. 

Academic scientists would of course go for a biological Proof of Principle. They would immediately delete the gene (i.e., make a knockout transgenic animal) and look for a phenotype. A Pharma company would, sooner or later, license this transgenic animal from the academic scientists to know if the compound they have made is specific. It should not work at all in the knockout animal if the drug is 100% specific since the target is not expressed and does not exist or occur in the knockout animal. The only interactions that should be present will be those responsible for causing side effects. This is very useful. 

Fig. 7.4. Production of homozygous knockout" transgenic mice throngh ES cell technology.

Plum L, Wunderlich FT, Baudler S et al (2005) Transgenic and knockout mice in diabetes research novel insights into pathophysiology, limitations, and perspectives. Physiology 20 152-161... 

As additional tools, transgenic mice overexpressing NPY and knockout mice lacking NPY, Yi receptors or Y5 receptors have been published. 

Douni E, Akassoglou K, Alexopoulou L, et al. Transgenic and knockout analyses of the role of TNF in immune regulation and disease pathogenesis. J Inflamm 1995 47(l-2) 27-38. 

Raeber AJ, Brandner S, Klein MA, Benninger Y, Musahl C, Frigg R, Roeckl C, Fischer MB, Weissmann C, Aguzzi A. Transgenic and knockout mice in research on prion diseases. Brain Pathol 1998 8 715-733. 

Eguchi, N., et at (2002). Sleep in transgenic and gene-knockout mice for... 

Other knockout models that could be used to validate candidate genes include mice that lack monoamine oxidase A (MAO-A), which have demonstrated altered behavior and alcohol tolerance [54]. Transgenic mice in which the dopamine transporter gene has been deleted show striking hyperactivity via enhanced persistence of dopamine which is not altered by cocaine or amphetamine administration [55]. Knockouts of the serotonin IB receptor are also available and are best used as models of vulnerability to drug abuse [56]. 

In contrast to LTP, LTD is induced by low-frequency stimulation. This causes the selective activation of PP2B (calcineurin), which maintains inhibitor-1 in its dephos-phorylated state. Several studies, including those using inhibitor-1 knockout mice and transgenic mice expressing a constitutively active form of inhibitor-1, demonstrate that the control of PP1 activity by inhibitor-1 in the hippocampus affects neuronal plasticity and learning and memory. 

Transgenic and knockout mice are employed to investigate the genetics of anxiety 900... 

---