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Research Article

Utrophin Up-Regulation by an Artificial Transcription Factor in Transgenic Mice

  • Elisabetta Mattei,

    Affiliations: Istituto di Neurobiologia e Medicina Molecolare, Consiglio Nazionale delle Ricerche, European Brain Research Institute, Rome, Italy, Italian Association for Cancer Research, Roman Oncogenomic Center, Rome, Italy

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  • Nicoletta Corbi,

    Affiliation: Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Regina Elena Cancer Institute, Rome, Italy

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  • Maria Grazia Di Certo,

    Affiliations: Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy, Istituto di Neurobiologia e Medicina Molecolare, Consiglio Nazionale delle Ricerche, European Brain Research Institute, Rome, Italy

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  • Georgios Strimpakos,

    Affiliation: Istituto di Neurobiologia e Medicina Molecolare, Consiglio Nazionale delle Ricerche, European Brain Research Institute, Rome, Italy

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  • Cinzia Severini,

    Affiliation: Istituto di Neurobiologia e Medicina Molecolare, Consiglio Nazionale delle Ricerche, European Brain Research Institute, Rome, Italy

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  • Annalisa Onori,

    Affiliation: Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Regina Elena Cancer Institute, Rome, Italy

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  • Agata Desantis,

    Affiliations: Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Regina Elena Cancer Institute, Rome, Italy, Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy

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  • Valentina Libri,

    Affiliation: Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Regina Elena Cancer Institute, Rome, Italy

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  • Serena Buontempo,

    Affiliation: Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Regina Elena Cancer Institute, Rome, Italy

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  • Aristide Floridi,

    Affiliations: Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy, Laboratory B, Regina Elena Cancer Institute, Rome, Italy

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  • Maurizio Fanciulli,

    Affiliations: Italian Association for Cancer Research, Roman Oncogenomic Center, Rome, Italy, Laboratory B, Regina Elena Cancer Institute, Rome, Italy

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  • Dilair Baban,

    Affiliation: Department of Physiology, Anatomy and Genetics, Medical Research Council Functional Genetics Unit, University of Oxford, Oxford, United Kingdom

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  • Kay E. Davies,

    Affiliation: Department of Physiology, Anatomy and Genetics, Medical Research Council Functional Genetics Unit, University of Oxford, Oxford, United Kingdom

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  • Claudio Passananti mail

    To whom correspondence should be addressed. E-mail: passananti@ifo.it

    Affiliations: Italian Association for Cancer Research, Roman Oncogenomic Center, Rome, Italy, Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Regina Elena Cancer Institute, Rome, Italy

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  • Published: August 22, 2007
  • DOI: 10.1371/journal.pone.0000774

Reader Comments (2)

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Referee Comments: Referee 1

Posted by PLoS_ONE_Group on 03 Sep 2007 at 00:11 GMT

Reviewer 1's Review

“In this manuscript, Mattei et al. examined utrophin up-regulation in transgenic mice expressing the artificial transcription factor VP16-Jazz. The major findings of this paper are: 1) generation and characterization of transgenic mice expressing the VP16-Jazz gene. 2) The effectiveness of the binding of Jazz protein to the endogenous utrophin promoter in mouse muscle. 3) Utrophin up-regulation in muscle.

Although these findings appear very interesting, there are some issues that need more investigation.
1) It is unclear whether utrophin up-regulation could affect the expression of other components of the dystrophin glycoprotein complex (dystrophin....) and whether the introduction of VP-Jazz gene could affect the expression of other proteins that may have similar binding sequences to utrophin
2) It is unclear whether the expression of utrophin at the synaptic site is up-regulated.
3) It would be informative to determine whether the localization of utrophin in the extrasynaptic region shown by immunofluorescence is a direct up-regulation of utrophin in the extrasynaptic site or a translocation of mRNA or protein from synaptic site into extrasynaptic zone.
4) It would be interesting to investigate utrophin in these transgenic mice during development as well as in muscle degeneration and regeneration.
5) The difference in contractile response and stimulation between diaphragm and EDL muscles needs to be discussed.”

N.B. These are the general comments made by the reviewer when reviewing the originally submitted version of this paper. The manuscript was revised before publication. Specific minor points addressed during revision of the paper are not shown.