Reviewer's report
Title:Lack of Guanylate Cyclase C results in increased mortality in mice
following liver injury
Version: 2Date:19 February 2010
Reviewer: Scott Swenson
Reviewer's report:
Guanylate cyclase C regulates fluid and electrolyte secretion in the intestine.
GCC is also expressed in neonatal and regenerating liver, where its function is
obscure. The authors tested the hypothesis that absence of GCC would be
deleterious in regenerating liver by administering carbon tetrachloride in knockout
animals compared with controls. They report here that susceptibility to carbon
tetrachloride liver injury and death was increased in GCC knockout mice, through
an increase in hepatocyte apoptosis in the knockout mice. However, the
increased susceptibility of GCC knockout mice was dependent on strain
background, indicating that other genes modify this phenotype.
The paper is well-written and the experiments straightforward. Apoptosis and
proliferation after CCl4 administration were measured by standard TUNEL
assays and PCNA immunostaining. Liver necrosis was quantitated using ImageJ
software. Transcripts for GCC and the ligands guanylin and uroguanylin were
measured by Sybr green quantitative RT-PCR.
The data are presented clearly and the conclusions are supported by the data. I
have no specific concerns which would require additional work.
Two questions that come to mind are:
1. Does the same increased susceptibility to liver injury in GCC knockout mice
occur with other liver injuries, such as partial hepatectomy or acetaminophen
toxicity?
2. Is there an increase in susceptibility to CCl4 or other liver toxins in guanylin or
uroguanylin knockout mice?
These questions may be addressed in future work.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Lack of Guanylate Cyclase C results in increased mortality in mice
following liver injury
Version: 2Date:19 February 2010
Reviewer: Scott Swenson
Reviewer's report:
Guanylate cyclase C regulates fluid and electrolyte secretion in the intestine.
GCC is also expressed in neonatal and regenerating liver, where its function is
obscure. The authors tested the hypothesis that absence of GCC would be
deleterious in regenerating liver by administering carbon tetrachloride in knockout
animals compared with controls. They report here that susceptibility to carbon
tetrachloride liver injury and death was increased in GCC knockout mice, through
an increase in hepatocyte apoptosis in the knockout mice. However, the
increased susceptibility of GCC knockout mice was dependent on strain
background, indicating that other genes modify this phenotype.
The paper is well-written and the experiments straightforward. Apoptosis and
proliferation after CCl4 administration were measured by standard TUNEL
assays and PCNA immunostaining. Liver necrosis was quantitated using ImageJ
software. Transcripts for GCC and the ligands guanylin and uroguanylin were
measured by Sybr green quantitative RT-PCR.
The data are presented clearly and the conclusions are supported by the data. I
have no specific concerns which would require additional work.
Two questions that come to mind are:
1. Does the same increased susceptibility to liver injury in GCC knockout mice
occur with other liver injuries, such as partial hepatectomy or acetaminophen
toxicity?
2. Is there an increase in susceptibility to CCl4 or other liver toxins in guanylin or
uroguanylin knockout mice?
These questions may be addressed in future work.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Lack of Guanylate Cyclase C results in increased mortality in mice
following liver injury
Version: 2Date:19 February 2010
Reviewer: Scott Swenson
Reviewer's report:
Guanylate cyclase C regulates fluid and electrolyte secretion in the intestine.
GCC is also expressed in neonatal and regenerating liver, where its function is
obscure. The authors tested the hypothesis that absence of GCC would be
deleterious in regenerating liver by administering carbon tetrachloride in knockout
animals compared with controls. They report here that susceptibility to carbon
tetrachloride liver injury and death was increased in GCC knockout mice, through
an increase in hepatocyte apoptosis in the knockout mice. However, the
increased susceptibility of GCC knockout mice was dependent on strain
background, indicating that other genes modify this phenotype.
The paper is well-written and the experiments straightforward. Apoptosis and
proliferation after CCl4 administration were measured by standard TUNEL
assays and PCNA immunostaining. Liver necrosis was quantitated using ImageJ
software. Transcripts for GCC and the ligands guanylin and uroguanylin were
measured by Sybr green quantitative RT-PCR.
The data are presented clearly and the conclusions are supported by the data. I
have no specific concerns which would require additional work.
Two questions that come to mind are:
1. Does the same increased susceptibility to liver injury in GCC knockout mice
occur with other liver injuries, such as partial hepatectomy or acetaminophen
toxicity?
2. Is there an increase in susceptibility to CCl4 or other liver toxins in guanylin or
uroguanylin knockout mice?
These questions may be addressed in future work.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
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