Knock-in mice

Gong, J.-S.,Kobayashi, M.,Hayashi,H. etal. Apolipoprotein E (apoE) isoform-dependent lipid release from astrocytes prepared from human apoE3 and apoE4 knock-in mice. /. Biol. Chem. 277 29919-29926, 2002. 

Knitgoods, dyeing, 0 171, 200, 201 Knitted fabrics, 24 619-620 Knitting, 11 178 cotton, 8 17-18 Knock, engine, 12 390-392 Knock-in mice, 12 462 Knock-out mice, 12 462 conditional, 12 467 Knock sensors, 12 394... 

AP has a very effective binding domain for copper in its N-terminal domain and can bind copper in nanomolar amounts (Figure 18.15). It is unclear whether APP or AP when associated with copper, are in fact neuronal metallochaperones. Knock out and knock in mice for APP show that in the former, cerebral cortex copper levels are increased, whereas in the latter reduced copper levels were found. Copper was also influential in APP processing in the cell copper will reduce levels of Ap and cause an increase in the secretion of the APP ectodomain. 

Wu J, George AA, Schroeder KM, Xu L, Marxer-MUler S, Lucero L, Lukas RJ (2004) Elec-trophysiological, pharmacological, and molecular evidence for alphaT-nicotinic acetylcholine receptors in rat midbrain dopamine neurons, J Pharmacol Exp Ther 311 80-91 Xu J, Lerraro NV, Zhu Y, Lonck C, Deshpande P, Marks MJ, Collins AC, Lester HA, Heinemann SL (2006) Increased sensitivity to nicotine-induced seizures in 32 V287L knock-in mice, Soc Neurosci Abstr 36 326,314/C382... 

Zwirner, J., Koentgen, F., Padkjaer, S., Mackay, F., Whitfield, P.L., and Mackay, C.IL (2006) Human C5aR knock-in mice facilitate the production and assessment of antiinflammatory monoclonal antibodies. Nat. Biotechnol. 24, 1279-1284. 

Identification of the actual genetic variants involved in disease is not a trivial task for complex diseases. Cross ethnic studies can aid in this venture, as patterns of LD may differ. Animal models also provide valuable information from study of knock-out and knock-in mice and from the mapping of QTLs in inbred strains. 

Stutzmann, G.E., Caccamo, A., LaFerla, F.M., and Parker, I., 2004, Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer s-linked mutation in presenilinl results in exaggerated Ca2+ signals and altered membrane excitability. J. Neurosci. 24 508-513. 

Sultana R, Robinson RA, Di Domenico F, Abdul HM, St Clair DK, Markesbery WR et al (2011) Proteomic identification of specifically carbonylated brain proteins in APPNLh/APPNLh x PS-1P264L/ PS-1P264L human double mutant knock-in mice model of Alzheimer disease as a function of age. J Proteomics 74 2430-2440... 

To create xenobiotic receptor knock-in mice that express the wild-type or activated xenobiotic nuclear receptors under the control of the endogenous/natural receptor promoters. The knock-in mice will allow normalization of the expression of the transgene to that of the endogenous/wild-type receptors. The knock-in may also help to reveal the function of receptors outside of the liver and intestine. 

---