Knockout mouse model

A key requirement of QSAR is that the compounds used in the modeling and prediction processes should have the same mechanism of action, and for this reason most QSAR studies are made with congeneric series of compounds. However, if a diverse set of compounds can reasonably be assumed to have the same mechanism of action, QSAR modeling can justihably be carried out. For example, Dearden et al. [43] developed a QSAR for the ratio of brain levels of 22 very diverse drugs in the wild-type mouse and the P-glycoprotein knockout mouse (R+/ ) ... 

Hu, W, Jiang, A, Liang, J, Meng, H, Chang, B, Gao, H, and Qiao, X, 2008. Expression of VLDLR in the retina and evolution of subretinal neovascularization in the knockout mouse model s retinal angiomatous proliferation. Invest Ophthalmol Vis Sci 49, 407 115. 

Although many animal models for iron overload exist, some mimicking certain aspects of HH, the 32-microglobulin knockout mouse is of special interest as it revealed for the first time crucial aspects of the pathogenesis of human HH in an animal model, and also because it underlines the important links between iron metabolism and the immune system. Hepatic iron overload in 32-microglobulin ( 32m)-deficient mice appeared to be similar to that found in HH, with pathological iron depositions occurring predominantly in liver parenchymal cells (de Sousa et ah,... 

Nelson We have the phospholamban knockout mouse model, and John Lederer was able to peel out a component of the decay that was due to reuptake. We didn t see any difference between the control and the knockouts. Presumably it is happening, but we couldn t see any difference in the decay in the phospholamban knockouts, as was seen in heart muscle, nor could we see any effect of lanthanum or zero Na+. Examining the decay of the spark would be a good indicator of local Ca2+ removal, though. It would also be worth examining the decay of the BK current. 

Gene-targeted (knockout) mouse models provide one avenue for assessing the in vivo functional significance of particular proteins. A complementary approach is the expression of the protein of interest using transgenic methodology. There... 

Doran, A., Obach, R. S., Smith, B. J., et al. (2005) The impact of P-glycoprotein on the disposition of drugs targeted for indications of the central nervous system evaluation using the MDRIA/IB knockout mouse model. Drug Metab. Dispos. 33, 165-174. 

Olivier B, Pattij T, Wood SJ, Oosting R, Sarnyai Z, Toth M (2001) The 5-HTlA receptor knockout mouse and anxiety. Behav Pharmacol 12 439-450 Overmier JB, Seligman MEP (1967) Effects of inescapable shock upon subsequent escape and avoidance learning. J Comp Physiol Psychol 63 28-33 Overstreet DH (1993) The Flinders sensitive line rats a genetic animal model of depression. Neurosci Biobehav Rev 17 51-68... 

Toth M (2003) 5-HT(lA) receptor knockout mouse as a genetic model of anxiety. Eur J Pharmacol 463 177-184... 

As mentioned above, impaired fluid absorption in kidney proximal tubule in AQPl deficiency indicates the need for high cell membrane water permeability for rapid, near-isosmolar fluid transport. The involvement of AQPs in fluid secretion by glands (salivary, submucosal, sweat, lacrimal), and by the choroid plexus and the ciliary body has been investigated using appropriate knockout mouse models. The general conclusion is that AQPs facilitate active fluid (secretion and absorption) when sufficiently rapid, in which case AQP deletion is associated with reduced volume and increased ion/solute content of secreted fluid. AQPs appear not to be needed when fluid secretion rate (per unit epithelial surface area) is low, as AQP-independent water permeability is high enough to support slow fluid secretion (or absorption). 

Jiang D., Akopian G., Ho Y. S., Walsh J. P, and Andersen J. K. (2000). Chronic brain oxidation in a glutathione peroxidase knockout mouse model results in increased resistance to induced epileptic seizures. Exp. Neurol. 164 257-268. 

The link between Cox-2 and polyps has been most extensively studied in an animal model of FAP, the adenomatous polyposis coli gene knockout mouse, which develops multiple intestinal polyps. In this model, both sulindac and a Cox-2 inhibitor are effective in producing regression of adenomas. When this knockout mouse was crossbred to a Cox-2 knockout mouse to produce a double adenomatous polyposis coli/Cox-2 knockout, the development of intestinal polyposis was markedly reduced (Oshima etal., 1996). 

Kadowaki, T. 2000. Insights into insulin resistance and type 2 diabetes from knockout mouse models. J Clin Invest 106 459-465. 

In 1998, Zhou and colleagues used an HFE knockout mouse model to elegantly bring together the pathophysiological and molecular aspects of the disease. Even when fed a standard diet, the knockout mice showed abnormally high transferrin saturations and excessive iron deposition in the liver and passed these traits on in an autosomally recessive manner. 

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