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closeReferee comments: Referee 1
Posted by PLOS_ONE_Group on 08 Feb 2008 at 21:33 GMT
Referee 1's review:
Summary
The authors have demonstrated a reduction of brown adipose tissue (BAT) in newborn PrlR-null mice, which correlated with reduced levels of TG as well as a decrease of UCP1. On a functions level, ko mice were more sensitive to cold, with death as a read out. Immortalized cell lines from PrlR-null mice were used to dissect the signaling pathway and the authors make a strong case that Prl through the activation of the jak/Stat5 pathway controls IGF-2 expression. Moreover, upon reintroduction of IGF-2 expression into cell lines, part of the PrlR associated defects can be rescued.
Critique
This is a convincing study and sheds new light on yet another role of prolactin in physiology. The authors make the claim that the reduction of IGF2 levels are the cause of the BAT dysfunction and that prolactin activates transcription of the IGF-2 gene through the Jak2/Stat5 pathway. This reviewer feels that it is necessary to provide additional evidence for the presence this pathway in BAT and the relevance to the PrlR-null phenotype. If the authors are correct, Stat5-null mice and IGF2-null mice should have a very similar phenotype, including smaller BAT with a suboptimal function. It would be necessary to analyze such mice, which should not be a problem since they are widely available. Secondly, it would be necessary to perform a ChIP assay to demonstrate the binding of Stat5 to GAS sites in the IGF2 gene in vivo, i.e. in BAT.
The authors describe the results as very novel. Enlighten me, what is the difference between novel and very novel?
The authors did not mention an animal protocol for the "cold sensitivity" study. Death is the endpoint in this study and an animal protocol needs to be listed.
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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.