Reviewer's report 
 Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen Title: 
 3  31 July 2006 Version: Date: 
 Miklos Sahin-Toth Reviewer: 
Reviewer's report: 
General 
This is a very important study, which demonstrates that low level transgenic expression of human cationic 
trypsinogen with the R122H mutation does not cause spontaneous pancreatitis in mice. Furthermore, the 
transgene does not sensitize the mice to artificially induced pancreatitis to a significant extent. What makes 
this report so valuable is that anecdotal reports about unsuccessful transgenic mouse models of hereditary 
pancreatitis have been circulating the pancreatic research community for years, but no data has ever been published. This study suggests that the R122H mutation per se is not sufficient to precipitate pancreatitis, but high level expression of the mutated trypsinogen is also necessary. Overall, the manuscript is well 
written, the results are clearly described and the small effect observed with the R122H mutation is not 
over-interpreted. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be 
reached) 
None. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
My only suggestion concerns data presentation. In Fig 2b, the legend does not match whatâ €™s shown on 
the picture. This needs to be corrected. In Fig 3, addition of more labels would help the reader. Thus, in lane 
1, labels should indicate â €œhuman cationic trypsinogenâ € and â €œhuman anionic trypsinogenâ €. On 
the right side of the picture, â €œmouse anionic trypsinogensâ € and â €œmouse cationic trypsinogenâ € 
should be indicated. The title of the picture says "blot" twice (immunoblot blot). 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
None. 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research interests Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
Reviewer's report 
 Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen Title: 
 3  31 July 2006 Version: Date: 
 Miklos Sahin-Toth Reviewer: 
Reviewer's report: 
General 
This is a very important study, which demonstrates that low level transgenic expression of human cationic 
trypsinogen with the R122H mutation does not cause spontaneous pancreatitis in mice. Furthermore, the 
transgene does not sensitize the mice to artificially induced pancreatitis to a significant extent. What makes 
this report so valuable is that anecdotal reports about unsuccessful transgenic mouse models of hereditary 
pancreatitis have been circulating the pancreatic research community for years, but no data has ever been published. This study suggests that the R122H mutation per se is not sufficient to precipitate pancreatitis, but high level expression of the mutated trypsinogen is also necessary. Overall, the manuscript is well 
written, the results are clearly described and the small effect observed with the R122H mutation is not 
over-interpreted. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be 
reached) 
None. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
My only suggestion concerns data presentation. In Fig 2b, the legend does not match whatâ €™s shown on 
the picture. This needs to be corrected. In Fig 3, addition of more labels would help the reader. Thus, in lane 
1, labels should indicate â €œhuman cationic trypsinogenâ € and â €œhuman anionic trypsinogenâ €. On 
the right side of the picture, â €œmouse anionic trypsinogensâ € and â €œmouse cationic trypsinogenâ € 
should be indicated. The title of the picture says "blot" twice (immunoblot blot). 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
None. 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research interests Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
Please review this paper.
user
Reviewer's report 
 Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen Title: 
 3  31 July 2006 Version: Date: 
 Miklos Sahin-Toth Reviewer: 
Reviewer's report: 
General 
This is a very important study, which demonstrates that low level transgenic expression of human cationic 
trypsinogen with the R122H mutation does not cause spontaneous pancreatitis in mice. Furthermore, the 
transgene does not sensitize the mice to artificially induced pancreatitis to a significant extent. What makes 
this report so valuable is that anecdotal reports about unsuccessful transgenic mouse models of hereditary 
pancreatitis have been circulating the pancreatic research community for years, but no data has ever been published. This study suggests that the R122H mutation per se is not sufficient to precipitate pancreatitis, but high level expression of the mutated trypsinogen is also necessary. Overall, the manuscript is well 
written, the results are clearly described and the small effect observed with the R122H mutation is not 
over-interpreted. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be 
reached) 
None. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
My only suggestion concerns data presentation. In Fig 2b, the legend does not match whatâ €™s shown on 
the picture. This needs to be corrected. In Fig 3, addition of more labels would help the reader. Thus, in lane 
1, labels should indicate â €œhuman cationic trypsinogenâ € and â €œhuman anionic trypsinogenâ €. On 
the right side of the picture, â €œmouse anionic trypsinogensâ € and â €œmouse cationic trypsinogenâ € 
should be indicated. The title of the picture says "blot" twice (immunoblot blot). 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
None. 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research interests Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
assistant