Maternal thyroid hormones are transcriptionally active during embryo-fetal development: results from a novel transgenic mouse model (Articolo in rivista)

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  • Maternal thyroid hormones are transcriptionally active during embryo-fetal development: results from a novel transgenic mouse model (Articolo in rivista) (literal)
Anno
  • 2009-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1111/j.1582-4934.2009.00947.x (literal)
Alternative label
  • Nucera C. 1, Muzzi P. 2 , Tiveron C. 3,4 , Farsetti A. 5,6 , La Regina F. 4 ,Foglio B. 2 , Shih S-C. 7, Moretti F. 6, Della Pietra L. 5, Mancini F. 6 , Sacchi A. 5, Trimarchi F. 8, Vercelli A. 2 , Pontecorvi A. 1 (2009)
    Maternal thyroid hormones are transcriptionally active during embryo-fetal development: results from a novel transgenic mouse model
    in Journal of Cellular and Molecular Medicine (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Nucera C. 1, Muzzi P. 2 , Tiveron C. 3,4 , Farsetti A. 5,6 , La Regina F. 4 ,Foglio B. 2 , Shih S-C. 7, Moretti F. 6, Della Pietra L. 5, Mancini F. 6 , Sacchi A. 5, Trimarchi F. 8, Vercelli A. 2 , Pontecorvi A. 1 (literal)
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  • 2417 (literal)
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  • 2435 (literal)
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  • 14 (literal)
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  • Accepted date: 9-Oct-09 DOI: 10.1111/j.1582-4934.2009.00947.x About DOI 2009 Oct 23 [Epub ahed of print] IF = 5.114 (literal)
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  • 10 (literal)
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  • ISI Web of Science (WOS) (literal)
  • PubMe (literal)
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  • 1. Endocrinology Unit, Molecular Endocrinology and Endocrine Cancers laboratory, Department of Internal Medicine, Medical School \"A. Gemelli\", Catholic University, Roma (Italy). 2. Department of Anatomy, Pharmacology and Forensic Medicine, University of Torino, Torino (Italy). 3. Telethon Center, Regina Elena Cancer Institute, Roma (Italy). 4. Foundation EBRI Rita Levi-Montalcini, Roma (Italy). 5. Department of Experimental Oncology, Regina Elena Cancer Institute, Roma (Italy). 6. Institute of Neurobiology and Molecular Medicine, CNR, Roma (Italy). 7. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA. 8. Endocrinology Unit, Clinical-Experimental Department of Medicine and Pharmacology, University of Messina, (Italy). (literal)
Titolo
  • Maternal thyroid hormones are transcriptionally active during embryo-fetal development: results from a novel transgenic mouse model (literal)
Abstract
  • Background: Even though several studies highlighted the role of maternal thyroid hormones (THs) during embryo-fetal development, direct evidence of their interaction with embryonic thyroid receptors (TRs) is still lacking. Design: We generated a transgenic mouse model ubiquitously expressing a reporter gene tracing TH action during development. We engineered a construct (TRE2×) containing two TH-responsive elements controlling the expression of the LacZ reporter gene, which encodes beta-galactosidase (²-gal). The specificity of the TRE2× activation by TH was evaluated in NIH3T3 cells by cotransfecting TRE2× along with TRs, retinoic or estrogen receptors in the presence of their specific ligands. TRE2× transgene was microinjected into the zygotes, implanted in pseudopregnant BDF1 mice, and transgenic mouse models were developed. ²-gal expression was assayed in tissue sections of transgenic mouse embryos at different stages of development. Results: In vitro, TRE2× transactivation was observed only following physiological T3 stimulation, mediated exclusively by TRs. In vivo, ²-gal staining, absent until embryonic day 9.5-10.5 (E9.5-E10.5), was observed as early as E11.5-E12.5 in different primordia (i.e. central nervous system, sense organs, intestine, etc.) of the TRE2× transgenic embryos, while the fetal thyroid function (FTF) was still inactive. Immunohistochemistry for TRs essentially colocalized with ²-gal staining. No ²-gal staining was detected in embryos of hypothyroid transgenic mice. Importantly, treatment with T3 in hypothyroid TRE2× transgenic mice rescued ²-gal expression. Conclusions: our results provide in vivo direct evidence that during embryonic life and before the onset of FTF, maternal THs are transcriptionally active through the action of embryonic TRs. This model may have clinical relevance and may be employed to design endpoint assays for new molecules affecting THs action. (literal)
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