Reviewer's report 
 Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen Title: 
 3  3 July 2006 Version: Date: 
 Claus Schaefer Reviewer: 
Reviewer's report: 
General 
The authors generated transgenic mice carrying the R122H mutation of the cationic trypsinogen gen. 
Furthermore, the authors investigated the phenotype of this mice under untreated and cerulein-stimulated conditions, both in a model of acute and chronic pancreatitis. This study focuses on a highly interesting mechanism. Unfortunatly, the transgenic mice carrying the R22H mutation of the trypsinogen gen failed to 
develop a spontaneous form of pancreatitis and showed only a slightly more severe form of pancreatitis. 
The experimental design of the study is excellent and the experiments are well performed. Nevertheless, there are some concerns about this study. ------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be 
reached) 
1. The authors show data that after induction of cerulein pancreatitis amylase and lipase were elevated. The 
data for the cytokine levels MCP-1 and IL-6 as well as for IL-10, IL12p70, TNF and IFN-gamma are general 
lacking. These data should be provided either in part by figures or more notable as a table. 
2. Page 9 third paragraph: the histological data and the score for the severety are not shown. Here, an 
proven example would be helpful. 
3. The authors show in figure 3 four control animals but only one trabsgenic animal. I'm wondering whether 
the authors have established only one transgenic line. Do all investigated animals show similar low levels of protein expression? 
4. Apoptosis and NFkappaB activation are crucial for the severity of experimental pancreatitis. Are there any 
differences between non-transgenic and transgenic animals? 
5. Figure 6a: Scores for edema, infiltration, vacuolization and necrosis from the two different animal groups 
should be shown. 
6. The discussion should be rewritten. The attempt should be, to discuss the results in the scientific context 
and not to summarize the results. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article of importance in its field 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  3 July 2006 Version: Date: 
 Claus Schaefer Reviewer: 
Reviewer's report: 
General 
The authors generated transgenic mice carrying the R122H mutation of the cationic trypsinogen gen. 
Furthermore, the authors investigated the phenotype of this mice under untreated and cerulein-stimulated conditions, both in a model of acute and chronic pancreatitis. This study focuses on a highly interesting mechanism. Unfortunatly, the transgenic mice carrying the R22H mutation of the trypsinogen gen failed to 
develop a spontaneous form of pancreatitis and showed only a slightly more severe form of pancreatitis. 
The experimental design of the study is excellent and the experiments are well performed. Nevertheless, there are some concerns about this study. ------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be 
reached) 
1. The authors show data that after induction of cerulein pancreatitis amylase and lipase were elevated. The 
data for the cytokine levels MCP-1 and IL-6 as well as for IL-10, IL12p70, TNF and IFN-gamma are general 
lacking. These data should be provided either in part by figures or more notable as a table. 
2. Page 9 third paragraph: the histological data and the score for the severety are not shown. Here, an 
proven example would be helpful. 
3. The authors show in figure 3 four control animals but only one trabsgenic animal. I'm wondering whether 
the authors have established only one transgenic line. Do all investigated animals show similar low levels of protein expression? 
4. Apoptosis and NFkappaB activation are crucial for the severity of experimental pancreatitis. Are there any 
differences between non-transgenic and transgenic animals? 
5. Figure 6a: Scores for edema, infiltration, vacuolization and necrosis from the two different animal groups 
should be shown. 
6. The discussion should be rewritten. The attempt should be, to discuss the results in the scientific context 
and not to summarize the results. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article of importance in its field 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  3 July 2006 Version: Date: 
 Claus Schaefer Reviewer: 
Reviewer's report: 
General 
The authors generated transgenic mice carrying the R122H mutation of the cationic trypsinogen gen. 
Furthermore, the authors investigated the phenotype of this mice under untreated and cerulein-stimulated conditions, both in a model of acute and chronic pancreatitis. This study focuses on a highly interesting mechanism. Unfortunatly, the transgenic mice carrying the R22H mutation of the trypsinogen gen failed to 
develop a spontaneous form of pancreatitis and showed only a slightly more severe form of pancreatitis. 
The experimental design of the study is excellent and the experiments are well performed. Nevertheless, there are some concerns about this study. ------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be 
reached) 
1. The authors show data that after induction of cerulein pancreatitis amylase and lipase were elevated. The 
data for the cytokine levels MCP-1 and IL-6 as well as for IL-10, IL12p70, TNF and IFN-gamma are general 
lacking. These data should be provided either in part by figures or more notable as a table. 
2. Page 9 third paragraph: the histological data and the score for the severety are not shown. Here, an 
proven example would be helpful. 
3. The authors show in figure 3 four control animals but only one trabsgenic animal. I'm wondering whether 
the authors have established only one transgenic line. Do all investigated animals show similar low levels of protein expression? 
4. Apoptosis and NFkappaB activation are crucial for the severity of experimental pancreatitis. Are there any 
differences between non-transgenic and transgenic animals? 
5. Figure 6a: Scores for edema, infiltration, vacuolization and necrosis from the two different animal groups 
should be shown. 
6. The discussion should be rewritten. The attempt should be, to discuss the results in the scientific context 
and not to summarize the results. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article of importance in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
assistant