Genetically modified mouse

The first data on genetically modified mice were reported very recently. Animals deficient in GPR4, OGR1, and TDAG8 are viable and fertile, and show no major defects. A short summary of available information is given in the following (see also Table 1). 

Studies with a variety of genetically modified mice have shed new light on the complex relationship between the protective and pathological immune responses controlling parasite infections. TNF and NO are important components of the pathological response accompanying the expulsion of a gastrointestinal nematode parasite. In the absence of TNF-R1 or iNOS, mice do not develop the severe villus atrophy and mucosal mastocytosis that usually accompany infection with T. spiralis, but their ability to expel the... 

Genetically modified mice and their importance in psychopharmacology... 

Gerlai 1996,2001). In such cases, animals have to be crossed with a pure inbred strain (commonly C57BL/6J hnes) for at least 6-8 generations (backcrossing). For correct interpretation of data obtained in genetically modified mice it is indispensable to follow the strict rules of strain nomenclature (Wotjak 2003). 

In two studies with genetically modified mice, there was no treatment-related increase in the incidence of tumours. 

Feil R, Lohmann SM, de Jonge H, et al. Cyclic GMP dependent protein kinases and the cardiovascular system insights from genetically modified mice. Circ Res. 2003 93 907-916. 

Key words Genetically modified mice, inbred mice, sperm cryopreservation, embryo cryopreservation, IVF, in vitro fertilization, genetic drift, genetic contamination. 

Cryan, J. F. and Mombereau, C. (2004) In search of a depressed mouse utility of models for studying depression-related behavior in genetically modified mice. Mol Psychiatry 9, 326-357. 

Superoxide dismutase turns out to be the key mammalian antioxidant enzyme. SOD is essential genetically modified mice lacking the enzyme die shortly after birth. It exists in several forms but the most closely studied version is SOD1, a protein containing zinc and copper. The catalytic site, shown in Fig. 4.11, contains a copper cation held by three neutral histidines and one histidine anion which in turn is bound to a zinc atom. 

The techniques that have proven most valuable in toxicology include those of molecular cloning, the polymerase chain reaction, and the production of genetically modified mice. Microarrays, used to evaluate gene expression under various conditions, including exposure to toxicants, are becoming more important and, in concert with other molecular techniques, are being considered as potentially useful in such applied areas as hazard assessment and risk analysis. 

In humans, chronic inflammation of the liver is associated with hepatitis B virus (HBV) infections, and this inflammation is considered an important contributing event in HBV-induced liver cancer. In animal models, there is evidence that inflammation contributes to tumor promotion. Treatment of mouse skin with TPA produces an inflammatory response and increases the expression of proinflammatory mediators such as TNF-a, IL-la GM-CSF, and cyclooxygenase-2 (COX-2). Genetically modified mice deficient in TNFa or COX-2 are resistant to TPA-induced tumor promotion. These results indicate that the inflammatory effects of TPA are important in tumor promotion. 

Genetically modified mice either overexpressing or knocking out specific components have provided exciting advances in our knowledge of diseases. Recently, we focused on the p38 mitogen-activated protein kinase (MAPK) pathway and its physiological effect on inflammation. 

The availability of genetically modified mice has advanced our understanding of several neurodegenerative processes. Cellular neurobiology experiments have informed us about mechanisms of neuronal dysfunction in AD and PD mouse models. For instance, recent studies have identified that synaptic transmission is one of the earliest events in the cognitive abnormalities that characterize AD and PD. The integration of this information with data-based circuits modeling, in which neuronal electrical properties, synaptic transmission parameters, and brain oscillations can now be evaluated and it has been recently addressed in PD and AD. 

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