Reviewer's report 
 Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen Title: 
 3  7 August 2006 Version: Date: 
 Martin Fernandez-Zapico Reviewer: 
Reviewer's report: 
In the article entitled â€œCharacterization of a transgenic mouse expressing R122H human cationic 
trypsinogenâ€  by Selig et al., the authors presented data describing the effect of expressing R122H 
human cationic trypsinogen mutant in pancreatic acinar cells using the rat elastase promoter. Interestingly, R122H transgenic mice were normal with no histologic difference with wild type control animals. No spontaneous development of pancreatitis, only an elevated pancreatic lipase was found in R122H mice. 
Induction of pancreatitis using cerulein resulted in a slightly more severe pancreatitis in R122H animals. 
However, amylase, lipase, and the cytokine levels were similar to controls. From these observations, the authors conclude that this little or no effect (failure to develop a spontaneous pancreatitis or slightly more severe cerulein-induced pancreatitis) was due to the low expression of the transgene in the mouse 
pancreas. These findings presented in this manuscript are potentially interesting and may give us some 
insight into the role of this mutation in pathogenesis of hereditary pancreatitis. However, the manuscript is still premature and requires the authors to further characterize the R122H transgenic animal before the manuscript is considered for publication in this journal. 
Major Revisions 
The authors recently published (BBRC 2005) that expression R122H mutant reduces cell viability and 
induces caspase-3 activity in acinar cells in vitro. These cellular and biochemical events must be explored 
in the transgenic animals. These experiments should be done under basal and stimulated conditions. 
Lack of differences in activation of the trypsionogen could be the explanation of this lack of phenotype. The 
trypsinogen expression should be accompanied by the level of activation of trypsinogen in control and 
transgenic animals under basal conditions or treatment with cerulein.Also, together with the levels of pancreatic enzymes under basal conditions, the authors should show the histology of the transgenic animals. 
Minor Revisions: 
The figures showing the establishment of the transgenic line (1, 2 and 3) should be incorporated into a single one. Results on the expression and integration of the transgene should be shown in more than one 
transgenic line. Also the quality of the picture should be improved in figure 2b as well as 3. Figure 2a legend 
requires a better description of the findings e.g. it is missing the description of line 1 and 2. 
 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: 
 Needs some language corrections before being published 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  7 August 2006 Version: Date: 
 Martin Fernandez-Zapico Reviewer: 
Reviewer's report: 
In the article entitled â€œCharacterization of a transgenic mouse expressing R122H human cationic 
trypsinogenâ€  by Selig et al., the authors presented data describing the effect of expressing R122H 
human cationic trypsinogen mutant in pancreatic acinar cells using the rat elastase promoter. Interestingly, R122H transgenic mice were normal with no histologic difference with wild type control animals. No spontaneous development of pancreatitis, only an elevated pancreatic lipase was found in R122H mice. 
Induction of pancreatitis using cerulein resulted in a slightly more severe pancreatitis in R122H animals. 
However, amylase, lipase, and the cytokine levels were similar to controls. From these observations, the authors conclude that this little or no effect (failure to develop a spontaneous pancreatitis or slightly more severe cerulein-induced pancreatitis) was due to the low expression of the transgene in the mouse 
pancreas. These findings presented in this manuscript are potentially interesting and may give us some 
insight into the role of this mutation in pathogenesis of hereditary pancreatitis. However, the manuscript is still premature and requires the authors to further characterize the R122H transgenic animal before the manuscript is considered for publication in this journal. 
Major Revisions 
The authors recently published (BBRC 2005) that expression R122H mutant reduces cell viability and 
induces caspase-3 activity in acinar cells in vitro. These cellular and biochemical events must be explored 
in the transgenic animals. These experiments should be done under basal and stimulated conditions. 
Lack of differences in activation of the trypsionogen could be the explanation of this lack of phenotype. The 
trypsinogen expression should be accompanied by the level of activation of trypsinogen in control and 
transgenic animals under basal conditions or treatment with cerulein.Also, together with the levels of pancreatic enzymes under basal conditions, the authors should show the histology of the transgenic animals. 
Minor Revisions: 
The figures showing the establishment of the transgenic line (1, 2 and 3) should be incorporated into a single one. Results on the expression and integration of the transgene should be shown in more than one 
transgenic line. Also the quality of the picture should be improved in figure 2b as well as 3. Figure 2a legend 
requires a better description of the findings e.g. it is missing the description of line 1 and 2. 
 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: 
 Needs some language corrections before being published 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  7 August 2006 Version: Date: 
 Martin Fernandez-Zapico Reviewer: 
Reviewer's report: 
In the article entitled â€œCharacterization of a transgenic mouse expressing R122H human cationic 
trypsinogenâ€  by Selig et al., the authors presented data describing the effect of expressing R122H 
human cationic trypsinogen mutant in pancreatic acinar cells using the rat elastase promoter. Interestingly, R122H transgenic mice were normal with no histologic difference with wild type control animals. No spontaneous development of pancreatitis, only an elevated pancreatic lipase was found in R122H mice. 
Induction of pancreatitis using cerulein resulted in a slightly more severe pancreatitis in R122H animals. 
However, amylase, lipase, and the cytokine levels were similar to controls. From these observations, the authors conclude that this little or no effect (failure to develop a spontaneous pancreatitis or slightly more severe cerulein-induced pancreatitis) was due to the low expression of the transgene in the mouse 
pancreas. These findings presented in this manuscript are potentially interesting and may give us some 
insight into the role of this mutation in pathogenesis of hereditary pancreatitis. However, the manuscript is still premature and requires the authors to further characterize the R122H transgenic animal before the manuscript is considered for publication in this journal. 
Major Revisions 
The authors recently published (BBRC 2005) that expression R122H mutant reduces cell viability and 
induces caspase-3 activity in acinar cells in vitro. These cellular and biochemical events must be explored 
in the transgenic animals. These experiments should be done under basal and stimulated conditions. 
Lack of differences in activation of the trypsionogen could be the explanation of this lack of phenotype. The 
trypsinogen expression should be accompanied by the level of activation of trypsinogen in control and 
transgenic animals under basal conditions or treatment with cerulein.Also, together with the levels of pancreatic enzymes under basal conditions, the authors should show the histology of the transgenic animals. 
Minor Revisions: 
The figures showing the establishment of the transgenic line (1, 2 and 3) should be incorporated into a single one. Results on the expression and integration of the transgene should be shown in more than one 
transgenic line. Also the quality of the picture should be improved in figure 2b as well as 3. Figure 2a legend 
requires a better description of the findings e.g. it is missing the description of line 1 and 2. 
 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: 
 Needs some language corrections before being published Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
assistant