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ABSTRACT _In vivo_ reporter gene and imaging technologies have the potential to contribute to the drug discovery pipeline in several areas. They provide systems that enable the study of the

biochemical activity of a target in disease, and in response to a drug, to be monitored over periods of time, and offer more accurate methods of measuring pharmacodynamics and toxicity.

Although reporter-gene technology is in its infancy, with further refinement reporter animals could become a valuable tool in the early stages of target and lead identification and

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our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS THE REGULATION OF REPORTER TRANSGENE EXPRESSION FOR DIVERSE BIOLOGICAL IMAGING APPLICATIONS Article Open access 04

March 2025 ZEBRAFISH DISEASE MODELS IN DRUG DISCOVERY: FROM PRECLINICAL MODELLING TO CLINICAL TRIALS Article 11 June 2021 TWENTY-FIRST CENTURY MOUSE GENETICS IS AGAIN AT AN INFLECTION POINT

Article Open access 26 November 2024 REFERENCES * Gershell, L. J. & Atkins, J. H. A brief history of novel drug discovery technologies. _Nature Rev. Drug Discov._ 2, 321–327 (2003).

Article  CAS  Google Scholar  * Zambrowicz, B. P. & Sands, A. T. Knockouts model the 100 best-selling drugs — will they model the next 100? _Nature Rev. Drug Discov._ 2, 38–51 (2003).

Article  CAS  Google Scholar  * Knowles, J. & Gromo, G. A guide to drug discovery: target selection in drug discovery. _Nature Rev. Drug Discov._ 2, 63–69 (2003) Article  CAS  Google

Scholar  * Wang, Y., DeMayo, F. J., Tsai, S. Y. & O'Malley, B. W. Ligand-inducible and liver-specific target gene expression in transgenic mice. _Nature Biotechnol._ 15, 239–243

(1997). Article  CAS  Google Scholar  * Solomin, L. et al. Retinoid-X receptor signalling in the developing spinal cord. _Nature_ 395, 398–402 (1998). Article  CAS  Google Scholar  * Mata De

Urquiza, A., Solomin, L. & Perlmann, T. Feedback-inducible nuclear-receptor-driven reporter gene expression in transgenic mice. _Proc. Natl Acad. Sci. USA_ 96, 13270–13275 (1999).

Article  CAS  Google Scholar  * Ciana, P. et al. Engineering of a mouse for the _in vivo_ profiling of estrogen receptor activity. _Mol. Endocrinol._ 15, 1104–1113 (2001). Article  CAS 

Google Scholar  * Nagel, S. C., Hagelbarger, J. L. & McDonnell, D. P. Development of an ER action indicator mouse for the study of estrogens, selective ER modulators (SERMs), and

xenobiotics. _Endocrinology_ 142, 4721–4728 (2001). Article  CAS  Google Scholar  * Rossant, J., Zirngibl, R., Cado, D., Shago, M. & Giguere, V. Expression of a retinoic acid response

element-hsplacZ transgene defines specific domains of transcriptional activity during mouse embryogenesis. _Genes Dev._ 5, 1333–1344 (1991). Article  CAS  Google Scholar  * Montoliu, L.,

Blendy, J. A., Cole, T. J. & Schutz, G. Analysis of perinatal gene expression: hormone response elements mediate activation of a lacZ reporter gene in liver of transgenic mice. _Proc.

Natl Acad. Sci. USA_ 92, 4244–4248 (1995). Article  CAS  Google Scholar  * Ciana, P. et al. _In vivo_ imaging of transcriptionally active estrogen receptors. _Nature Med._ 9, 82–86 (2003).

Article  CAS  Google Scholar  * Fukumura, D. et al. Tumor induction of VEGF promoter activity in stromal cells. _Cell_ 94, 715–725 (1998). Article  CAS  Google Scholar  * Lyons, S. K.,

Meuwissen, R., Krimpenfort, P. & Berns A. The generation of a conditional reporter that enables bioluminescence imaging of Cre/loxP-dependent tumorigenesis in mice. _Cancer Res._ 63,

7042–7046 (2003). CAS  PubMed  Google Scholar  * Yamaguchi, M., Saito, H., Suzuki, M. & Mori, K. Visualization of neurogenesis in the central nervous system using nestin promoter-GFP

transgenic mice. _Neurorep._ 11, 1991–1996 (2000). Article  CAS  Google Scholar  * Schmidt-Ullrich, R. et al. NF-κB activity in transgenic mice: developmental regulation and tissue

specificity. _Development_ 122, 2117–2128 (1996). CAS  PubMed  Google Scholar  * Carlsen, H., Moskaug, J. O., Fromm, S. H. & Blomhoff, R. In vivo imaging of NF-κB activity. _J. Immunol._

168, 1441–1446 (2002). Article  CAS  Google Scholar  * Huang, C. et al. Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the

antitumor promotion effect of retinoic acid. _Proc. Natl Acad. Sci. USA_ 94, 5826–5830 (1997). Article  CAS  Google Scholar  * Bruning, J. C. et al. Development of a novel polygenic model of

NIDDM in mice heterozygous for IR and IRS-1 null alleles. _Cell_ 88, 561–572 (1997). Article  CAS  Google Scholar  * Su, L. -K. et al. Multiple intestinal neoplasia caused by a mutation in

the murine homolog of the APC gene. _Science_ 256, 668–670 (1992). Article  CAS  Google Scholar  * DiMasi, J. A., Hansen, R. W. & Grabowski, H. G. The price of innovation: new estimates

of drug development costs. _J. Health Econ._ 22, 151–185 (2003). Article  Google Scholar  * Preziosi, P. Science, pharmacoeconomics and ethics in drug R&D: a sustainable future scenario?

_Nature Rev. Drug Discov._ 3, 521–526 (2004). Article  CAS  Google Scholar  * Geiling, E. M. K. & Cannon, P. R. Pathologic effects of elixir of sulphanilamide (diethylene glicol)

poisoning. _JAMA_ 111, 919–926 (1938). Article  CAS  Google Scholar  * Rawlins, M. D. Cutting the cost of drug development? _Nature Rev. Drug Discov._ 3, 360–364 (2004). Article  CAS  Google

Scholar  * Freireich, E. J., Gehan, E. A., Rall, D. P., Schmidt, L. H. & Skipper, H. E. Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and

man. _Cancer Chemother. Rep._ 50, 219–244 (1966). CAS  PubMed  Google Scholar  * Xie, W. & Evans, R. M. Pharmaceutical use of mouse models humanized for the xenobiotic receptor. _Drug

Discov. Today_ 7, 509–515 (2002). Article  CAS  Google Scholar  * Kenakin, T. Predicting therapeutic value in the lead optimization phase of drug discovery. _Nature Rev. Drug Discov._ 2,

429–438 (2003). Article  CAS  Google Scholar  * Verkhusha, V. V. & Lukyanov, K. A. The molecular properties and applications of Anthozoa fluorescent proteins and chromoproteins. _Nature

Biotechnol._ 22, 289–296 (2004). Article  CAS  Google Scholar  * Dmitriy, M. et al. Kindling fluorescent proteins for precise _in vivo_ photolabeling. _Nature Biotechnol._ 21, 191–194

(2003). Article  Google Scholar  * Paulmurugan, R. et al. Noninvasive imaging of protein-protein interactions in living subjects by using reporter protein complementation and reconstitution

strategies. _Proc. Natl Acad. Sci. USA_ 99, 15608–15613 (2002). Article  CAS  Google Scholar  * Willard, F. S. et al. Fluorescence-based assays for RGS box function. _Methods Enzymo._ 389,

56–71 (2004). Article  CAS  Google Scholar  * Ray, P. et al. Noninvasive quantitative imaging of protein–protein interactions in living subjects. _Proc. Natl Acad. Sci. USA_ 99, 3105–3110

(2002). Article  CAS  Google Scholar  * Massoud, T. F. & Gambhir, S. S. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. _Genes Dev._ 17,

545–580 (2003). Article  CAS  Google Scholar  * Contag, C. H. & Bachmann, M. H. Advances in _in vivo_ bioluminescence imaging of gene expression. _Annu. Rev. Biomed. Eng._ 4, 235–60

(2002). Article  CAS  Google Scholar  * Hadjantonakis, A. K., Dickinson, M. E., Fraser, S. E. & Papaioannou, V. E. Technicolour transgenics: imaging tools for functional genomics in the

mouse. _Nature Rev. Genet._ 4, 613–625 (2003). Article  CAS  Google Scholar  * Louie, A. Y. et al. _In vivo_ visualization of gene expression using magnetic resonance imaging. _Nature

Biotechnol._ 18, 321–325 (2000). Article  CAS  Google Scholar  * Moore, A. et al. Human transferrin receptor gene as a marker gene for MR imaging. _Radiology._ 221, 244–250 (2001). Article 

CAS  Google Scholar  * Liang, Q. et al. Noninvasive imaging of reporter gene expression in living subjects. _Adv. Cancer Res._ 92, 29–80 (2004). Article  Google Scholar  * Rudin, M. &

Weissleder, R. Molecular imaging in drug discovery and development. _Nature Rev. Drug Discov._ 2, 123–131 (2003). Article  CAS  Google Scholar  * Di Lorenzo, D. et al. Isomer specific

activity of DDT with estrogen receptor in adult and sucling mice. _Endocrinology_ 143, 4544–4551 (2002). Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Department of Pharmacological Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, Milan, 20133, Italy Adriana Maggi & 

Paolo Ciana Authors * Adriana Maggi View author publications You can also search for this author inPubMed Google Scholar * Paolo Ciana View author publications You can also search for this

author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Adriana Maggi. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. RELATED

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Ciana, P. Reporter mice and drug discovery and development. _Nat Rev Drug Discov_ 4, 249–255 (2005). https://doi.org/10.1038/nrd1661 Download citation * Issue Date: 01 March 2005 * DOI:

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