Abstract
Noninvasive, imaging-based methodologies provide for the first time the possibility to spatio-temporally investigate physiopathological events and long-term effects of drug administration of exposure to environmental and alimentary toxic compounds. Hence, this novel methodology could enable us to measure the dynamics of specific molecular pathways in live animals. In the last few years, animals, particularly mice, were genetically modified to respond to a specific stimulus with the production of proteins, named “reporters,” that are easily detected and quantitated by in vivo and ex vivo imaging. These “reporter mice” are gradually being applied to the pharmaco-toxicological research. In the generation of a reporter mouse useful for pharmaco-toxicological studies several elements need to be considered in the selection of the reporter system: the half-life of proteins should be compatible with the necessities of the study to assess the onset and the termination of the stimulus of interest, in all tissues the response should be proportional to the given stimulus, and the imaging modalities requested for reporter measurements should be applicable to high-throughput screening. Bioluminescence-based imaging (BLI) in small animals has the advantage over other modalities that does not require too sophisticated equipment or specifically and highly trained personnel, and furthermore may be carried out at a relative rapidity and low cost; for these reasons several luciferases have been developed for in vivo imaging applications and used in the generation of reporter mice. We here describe a BLI-based reporter mouse created to respond to estrogenic stimuli, which has been applied to the study of female physiopathology as well as for the identification of the effects of selective drugs or toxic compounds present in the environment and in the alimentary chain.
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References
Ciana P et al (2001) Engineering of a mouse for the in vivo profiling of estrogen receptor activity. Mol Endocrinol 15:1104–1113
Lemmen JG et al (2004) Tissue-and time-dependent estrogen receptor activation in estrogen reporter mice. J Mol Endocrinol 32:689–701
Ciana P et al (2007) A novel peroxisome proliferator-activated receptor responsive element-luciferase reporter mouse reveals gender specificity of peroxisome proliferator-activated receptor activity in liver. Mol Endocrinol 21:388–400
Ciana P et al (2003) In vivo imaging of transcriptionally active estrogen receptors. Nat Med 9:82–86
Biserni A et al (2008) In vivo imaging reveals selective peroxisome proliferator activated receptor modulator activity of the synthetic ligand 3-(1-(4-chlorobenzyl)-3-t-butylthio-5-isopropylindol-2-yl)-2,2-dimethylpropanoic acid (MK-886). Mol Pharmacol 73:1434–1443
Rando G et al (2009) Differential effect of pure isoflavones and soymilk on estrogen receptor activity in mice. Toxicol Appl Pharmacol 237:288–297
Ramachandran B et al (2011) Estrogen-like effects of diet-derived cadmium differ from those of orally administered CdCl(2) in the ERE-luc estrogen reporter mouse model. Toxicol Lett 202:75–84
Stell A et al (2008) Molecular imaging provides novel insights on estrogen receptor activity in mouse brain. Mol Imaging 7:283–292
Gorski RA (1971) Gonadal hormones and the perinatal development of neuroendocrine function. In: Martini L, Ganong WF (eds) Frontiers in neuroendocrinology. Oxford University Press, New York, pp 237–290
Della TS et al (2011) Amino acid-dependent activation of liver estrogen receptor alpha integrates metabolic and reproductive functions via IGF-1. Cell Metab 13:205–214
Villa A et al (2012) Tetradian oscillation of estrogen receptor α is necessary to prevent liver lipid deposition. Proc Natl Acad Sci U S A 109:11806–11811
Rando G et al (2010) An innovative method to classify SERMs based on the dynamics of estrogen receptor transcriptional activity in living animals. Mol Endocrinol 24:735–744
Della TS et al (2011) The conundrum of estrogen receptor oscillatory activity in the search for an appropriate hormone replacement therapy. Endocrinology 152:2256–2265
Di Lorenzo D et al (2002) Isomer-specific activity of dichlorodyphenyltrichloroethane with estrogen receptor in adult and suckling estrogen reporter mice. Endocrinology 143:4544–4551
Montani C et al (2008) Genistein is an efficient estrogen in the whole-body throughout mouse development. Toxicol Sci 103:57–67
Acknowledgements
The authors are grateful to the European Community for the significant and continued contribution to the work here shown with grant support: NoE DIMI (LSHB CT 2005 512146); Strep EWA (LSHM CT 2005 518245); WAYS (ERC-2012-AdG 322977).
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Rizzi, N., Ramachandran, B., Vantaggiato, C., Ciana, P., Maggi, A. (2014). Reporter Mice for the Study of Long-Term Effects of Drugs and Toxic Compounds. In: Castoria, G., Auricchio, F. (eds) Steroid Receptors. Methods in Molecular Biology, vol 1204. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-1346-6_5
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DOI: https://doi.org/10.1007/978-1-4939-1346-6_5
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