Genetically engineered mice

For more than 40 years, the most frequently used anxiolytic compounds have been benzodiazepines. Benzodiazepine agonists such as diazepam act via modulation of y-aminobutyric acidergic (GABAergic) transmission at GABAa receptors (see chapter by Duman and Duman, this volume), which consist of about 20 subunits. Several mutant mice with deletions of different subunits have been engineered (Holmes 2001) and most of these mutants perform altered anxiety-related behavior, thus emphasizing the intimate link between benzodiazepine receptors and anxiety. 

Another major focus of interest for the investigation of anxiety disorders is the monoamine neurotransmitter serotonin (5-HT see also chapter by Mohler et al., this volume) because of reduced levels of 5-HT receptors found in patients 

Taking into account the central role of the HPA-axis for the regulation of anxiety, a variety of genetically altered mice has been developed, aimed at targeting the hormonal stress system (Muller and Keck 2002 Sillaber et al. 2002 Stenzel-Poore et al. 1992 Timpl et al. 1998). These models are described extensively in the chapter by Keck and Muller and will, therefore, be omitted here. 

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Muller MB, Keck ME (2002) Genetically engineered mice for studies of stress-related clinical conditions. J Psychiatr Res 36 53-76... 

Crabbe JC et al Alcohol-related genes Contributions from studies with genetically engineered mice. Addict Biol 2006 11 195. [PMID 16961758]... 

Sundberg, J. P. and Ichiki, T. (2005) Genetically engineered mice handbook. CRC Press, Boca Raton. 

Ward, J., Mahler, J., Maronpot, R. and Sundberg, J. P. (2000) Pathology of genetically engineered mice. Iowa State University Press, Ames. 

Schofield, P. N., Bard, J. B. L., Rozell, B. and Sundberg, J. P. (2005) Computational pathology challenges in the informatics of phenotype description in mutant mice, in Handbook on genetically engineered mice (Sundberg, J. P. and Ichiki, T., eds.). CRC Press, Boca Raton, pp. 61-81. 

Doetschman T. Interpretation of phenotype in genetically engineered mice. Lab Animal Sci 1999 49 137-43. 

Bolon B, Galbreath EJ. Use of genetically engineered mice in drug discovery and development wielding Occam s razor to prune the product portfolio. Int J Toxicol 2002 21 55-64. 

Note Several papers utilize tumor cell implants into knockout or transgenic mice with associated changes in metastatic potential (Araki et al., 1997 Bian-cone et al., 1996 Bourguignon et al., 1998 Davies et al., 1996 De Vries et al., 1995 Driessens et al., 1995 Eitzman et al., 1996 Goldfarb et al., 1998 Hall and Thompson 1997 Kruger et al., 1998 Lloyd et al., 1998 Marvin et al., 1998). The citations listed above are those in which metastases are observed in the genetically engineered mice without inoculation of tumor cells. 

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