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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.