Reviewer's report 
 Differential gene expression profile in the small intestines of mice lacking pacemaker Title: 
interstitial cells of Cajal
Authors: 
Yataro Daigo ( yd206@cam.ac.uk )
Dr Ichiro Takayama ( ichirot@is.icc.u-tokai.ac.jp )
Prof Bruce AJ Ponder ( bajp@mole.bio.cam.ac.uk )
Dr Carlos Caldas ( cc234@cam.ac.uk )
Sean M Ward ( sean@physio.unr.edu )
Kenton M Sanders ( kent@physio.unr.edu )
Masayuki A Fujino ( mfujino@res.yamanashi-med.ac.jp )
 1  4 Apr 2003 Version: Date: 
 Heather Young Reviewer: 
 not specified Level of interest: 
 Other (see below) Advice on publication: 
Comments for authors: 
This study extends an earlier study that identified 8 genes that are differentially expressed in W/Wv 
mice. In the current study, an additional 7 genes were identified, of which 5 are novel transcripts. Differential gene display has the potential to identify important genes involved in the changes associated with loss of specific populations of ICC in the gut, and therefore studies such as that by 
Daigo et al. are important. 
The following points require attention (compulsory revisions): (a) What was the total number of genes found to be differentially expressed between W/Wv and 
wild-type in the original differential gene display? 
(b) Were the 8 genes identified in the previous study (published in "Gut" last year) those that showed 
the biggest differences in levels of expression, and are the 7 genes described in the current study 
also amongst the genes showing the biggest differences in levels of expression? 
(c) How many of the total number of genes found to be differentially expressed are the authors 
intending to identify in the future? 
(d) The last three sentences of the first paragraph of the Results summarize the data published in 
the 2002 "Gut" paper, and hence belong in the "Background" section rather than the "Results". 
(e) The Discussion of the role of the cytokine, LIF, is inadequate. LIF is a multifunctional cytokine 
implicated in various functions. LIF can play a role in neuroimmune reactions, but it also plays an 
important role in aspects of neuronal development, including phenotype determination, survival, and 
in response to nerve injury - these functions are independent of LIF's role in the immune system. In 
the Discussion the authors should have discussed whether LIF-deficient mice have been reported to 
show any gut phenotype, and whether LIF is expressed by the gut, and if so, by what cell types? 
Also there is no reference cited for the statement in the Discussion that "ONZIN was identified 
through a screening of LIF regulated genes". 
Minor points 
(a) should be "showed an increase" in the second last sentence of the Results section of the 
Abstract. 
(b) Should be "Loss of ICC has been reported" in the first sentence of the second paragraph of the 
Background. 
Competing interests: 
None declared. 
Reviewer's report 
 Differential gene expression profile in the small intestines of mice lacking pacemaker Title: 
interstitial cells of Cajal
Authors: 
Yataro Daigo ( yd206@cam.ac.uk )
Dr Ichiro Takayama ( ichirot@is.icc.u-tokai.ac.jp )
Prof Bruce AJ Ponder ( bajp@mole.bio.cam.ac.uk )
Dr Carlos Caldas ( cc234@cam.ac.uk )
Sean M Ward ( sean@physio.unr.edu )
Kenton M Sanders ( kent@physio.unr.edu )
Masayuki A Fujino ( mfujino@res.yamanashi-med.ac.jp )
 1  4 Apr 2003 Version: Date: 
 Heather Young Reviewer: 
 not specified Level of interest: 
 Other (see below) Advice on publication: 
Comments for authors: 
This study extends an earlier study that identified 8 genes that are differentially expressed in W/Wv 
mice. In the current study, an additional 7 genes were identified, of which 5 are novel transcripts. Differential gene display has the potential to identify important genes involved in the changes associated with loss of specific populations of ICC in the gut, and therefore studies such as that by 
Daigo et al. are important. 
The following points require attention (compulsory revisions): (a) What was the total number of genes found to be differentially expressed between W/Wv and 
wild-type in the original differential gene display? 
(b) Were the 8 genes identified in the previous study (published in "Gut" last year) those that showed 
the biggest differences in levels of expression, and are the 7 genes described in the current study 
also amongst the genes showing the biggest differences in levels of expression? 
(c) How many of the total number of genes found to be differentially expressed are the authors 
intending to identify in the future? 
(d) The last three sentences of the first paragraph of the Results summarize the data published in 
the 2002 "Gut" paper, and hence belong in the "Background" section rather than the "Results". 
(e) The Discussion of the role of the cytokine, LIF, is inadequate. LIF is a multifunctional cytokine 
implicated in various functions. LIF can play a role in neuroimmune reactions, but it also plays an 
important role in aspects of neuronal development, including phenotype determination, survival, and 
in response to nerve injury - these functions are independent of LIF's role in the immune system. In 
the Discussion the authors should have discussed whether LIF-deficient mice have been reported to 
show any gut phenotype, and whether LIF is expressed by the gut, and if so, by what cell types? 
Also there is no reference cited for the statement in the Discussion that "ONZIN was identified 
through a screening of LIF regulated genes". 
Minor points 
(a) should be "showed an increase" in the second last sentence of the Results section of the 
Abstract. 
(b) Should be "Loss of ICC has been reported" in the first sentence of the second paragraph of the 
Background. 
Competing interests: 
None declared. 
Please review this paper.
user
Reviewer's report 
 Differential gene expression profile in the small intestines of mice lacking pacemaker Title: 
interstitial cells of Cajal
Authors: 
Yataro Daigo ( yd206@cam.ac.uk )
Dr Ichiro Takayama ( ichirot@is.icc.u-tokai.ac.jp )
Prof Bruce AJ Ponder ( bajp@mole.bio.cam.ac.uk )
Dr Carlos Caldas ( cc234@cam.ac.uk )
Sean M Ward ( sean@physio.unr.edu )
Kenton M Sanders ( kent@physio.unr.edu )
Masayuki A Fujino ( mfujino@res.yamanashi-med.ac.jp )
 1  4 Apr 2003 Version: Date: 
 Heather Young Reviewer: 
 not specified Level of interest: 
 Other (see below) Advice on publication: 
Comments for authors: 
This study extends an earlier study that identified 8 genes that are differentially expressed in W/Wv 
mice. In the current study, an additional 7 genes were identified, of which 5 are novel transcripts. Differential gene display has the potential to identify important genes involved in the changes associated with loss of specific populations of ICC in the gut, and therefore studies such as that by 
Daigo et al. are important. 
The following points require attention (compulsory revisions): (a) What was the total number of genes found to be differentially expressed between W/Wv and 
wild-type in the original differential gene display? 
(b) Were the 8 genes identified in the previous study (published in "Gut" last year) those that showed 
the biggest differences in levels of expression, and are the 7 genes described in the current study 
also amongst the genes showing the biggest differences in levels of expression? 
(c) How many of the total number of genes found to be differentially expressed are the authors 
intending to identify in the future? 
(d) The last three sentences of the first paragraph of the Results summarize the data published in 
the 2002 "Gut" paper, and hence belong in the "Background" section rather than the "Results". 
(e) The Discussion of the role of the cytokine, LIF, is inadequate. LIF is a multifunctional cytokine 
implicated in various functions. LIF can play a role in neuroimmune reactions, but it also plays an 
important role in aspects of neuronal development, including phenotype determination, survival, and 
in response to nerve injury - these functions are independent of LIF's role in the immune system. In 
the Discussion the authors should have discussed whether LIF-deficient mice have been reported to 
show any gut phenotype, and whether LIF is expressed by the gut, and if so, by what cell types? 
Also there is no reference cited for the statement in the Discussion that "ONZIN was identified 
through a screening of LIF regulated genes". 
Minor points 
(a) should be "showed an increase" in the second last sentence of the Results section of the 
Abstract. 
(b) Should be "Loss of ICC has been reported" in the first sentence of the second paragraph of the 
Background. 
Competing interests: 
None declared. 
assistant