Mouse Models for Drug Discovery pp 79-92

Part of the Methods in Molecular Biology book series (MIMB, volume 602)

Profiling of Drug Action Using Reporter Mice and Molecular Imaging

  • Gianpaolo Rando
  • Andrea Biserni
  • Paolo Ciana
  • Adriana Maggi

Abstract

Reporter mice associated to molecular imaging represent a major asset for the study of the spatio-temporal effects of drugs in living animals. The field is still relatively young and so far the number of animals genetically modified to express a given reporter gene ubiquitously and under the control of specific drugs is still limited. For a reporter animal the indispensable elements for the application to drug research and development are (i) the short life of the reporter enabling to have a clear view of the onset as well as the termination of drug effects, (ii) the generalized, drug-dependent activation of the reporter, and (iii) imaging modality suitable for high-throughput analysis. Because of its relative cheapness and ease to perform, in addition to all the above considerations, bioluminescence-based imaging is now regarded as the best imaging technology to be applied to the field of drug research. We show here the application of reporter mouse systems for drug screening in living animals in order to compare drug potency on target and specificity of action.

Key words

Reporter mouse pharmacodynamics pharmacokinetics bioluminescence imaging ERE-Luc PPRE-Luc luciferase brain imaging 

References

  1. 1.
    Ciana P, Di Luccio G, Belcredito S, Pollio G, Vegeto E, Tatangelo L, Tiveron C, Maggi A. (2001) Engineering of a mouse for the in vivo profiling of estrogen receptor activity. Mol Endocrinol. 15(7), 1104–13.PubMedCrossRefGoogle Scholar
  2. 2.
    Ciana P, Biserni A, Tatangelo L, Tiveron C, Sciarroni AF, Ottobrini L, Maggi A. (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(2), 388–400.PubMedCrossRefGoogle Scholar
  3. 3.
    Ciana P, Raviscioni M, Mussi P, Vegeto E, Que I, Parker MG, Lowik C, Maggi A. (2003) In vivo imaging of transcriptionally active estrogen receptors. Nat Med. 9(1), 82–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Biserni A, Giannessi F, Sciarroni AF, Milazzo FM, Maggi A, Ciana P. (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(5), 1434–43.PubMedCrossRefGoogle Scholar
  5. 5.
    Stell A, Belcredito S, Ciana P, Maggi A. (2008) Molecular imaging provides novel insights on estrogen receptor activity in mouse brain. Mol Imaging. 7(6), 283–92.PubMedGoogle Scholar
  6. 6.
    Ibarra C, Bertocchi I, Ciana P, Biserni A, Eva C, Maggi A. (2009) Gender-dimorphic activity of brain PPARs in response to changes in the nutritional status (unpublished results).Google Scholar
  7. 7.
    Bouchard MB, MacLaurin SA, Dwyer PJ, Mansfield J, Levenson R, Krucker T. (2007) Technical considerations in longitudinal multispectral small animal molecular imaging. J Biomed Opt. 12(5), 051601.PubMedCrossRefGoogle Scholar
  8. 8.
    Szarecka A, Xu Y, Tang P. (2007) Dynamics of firefly luciferase inhibition by general anesthetics: Gaussian and anisotropic network analyses. Biophys J. 93(6), 1895–905.PubMedCrossRefGoogle Scholar
  9. 9.
    Cui K, Xu X, Zhao H, Wong S. (2008) A quantitative study of factors affecting in vivo bioluminescence imaging. Luminescence 23, 292–95.PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang Y, Bressler JP, Neal J, Lal B, Bhang HE, Laterra J, Pomper MG. (2007) ABCG2/BCRP expression modulates D-luciferin based bioluminescence imaging. Cancer Res. 67(19), 9389–97.PubMedCrossRefGoogle Scholar
  11. 11.
    Rando G, Casiraghi E, Arca S, Campadelli P, Maggi A. (2009) Automatic segmentation of mouse images. In: Stereology and Image Analysis. Ecs10-Proceedings of the 10th European Congress of ISS, (V.Capasso et al. Eds.), The MIRIAM Project Series, ESCULAPIO Pub. Co., p.60.Google Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Gianpaolo Rando
    • 1
  • Andrea Biserni
    • 2
  • Paolo Ciana
    • 1
  • Adriana Maggi
    • 3
  1. 1.Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological SciencesUniversity of MilanMilanItaly
  2. 2.TOP s.r.l.LodiItaly
  3. 3.Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological SciencesUniversità degli Studi di MilanoMilanItaly

Personalised recommendations