Reviewer's report
Title:Lack of Guanylate Cyclase C results in increased mortality in mice
following liver injury
Version: 2Date:9 March 2010
Reviewer: Arndt Vogel
Reviewer's report:
Mann et al. analyzed the role of guanylate cyclase C for CCL4 induced liver
injury in mice . They found that GC-C mice in a mixed background display a
increased mortality following a singly CCL4 injection. This effect was not seen in
mice with a pure C57 background. The work addresses an interesting issue in
principle, but the value of this study in its current form is limited. Overall, the data
provided so far are preliminary. Furthermore the manuscript is very descriptive
the exact mechanisms of the observed effects remain unclear.
Major comments:
- The apoptosis data are so far not very convincing. Personally, I do not think that
CCL4 induces apoptosis at all. The authors need to employ additional assays
such as caspase-3 activity by Western blot, activity assay and
immunohistochemistry to convincingly show that there is apoptosis following
CCL4. TUNEL staining is not at all specific for apoptosis. The authors should
also do TUNEL staining at later staining; they will actually see an further increase
in TUNEL positive cells.
- I actually do not understand why the mice gain weight during the first days after
CCL4 injection. Some of the mice almost double their relative liver weight. I
hardly believe that this is the result of liver regeneration. Do the mice loose
weight or do the really again liver weight?
- Why do the KO mice die still die at day 5-9? As shown by the authors liver
injury resolves after 2-3 days following CCL4 challenge and liver regeneration is
obviously not severely impaired in the KO mice.
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
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:9 March 2010
Reviewer: Arndt Vogel
Reviewer's report:
Mann et al. analyzed the role of guanylate cyclase C for CCL4 induced liver
injury in mice . They found that GC-C mice in a mixed background display a
increased mortality following a singly CCL4 injection. This effect was not seen in
mice with a pure C57 background. The work addresses an interesting issue in
principle, but the value of this study in its current form is limited. Overall, the data
provided so far are preliminary. Furthermore the manuscript is very descriptive
the exact mechanisms of the observed effects remain unclear.
Major comments:
- The apoptosis data are so far not very convincing. Personally, I do not think that
CCL4 induces apoptosis at all. The authors need to employ additional assays
such as caspase-3 activity by Western blot, activity assay and
immunohistochemistry to convincingly show that there is apoptosis following
CCL4. TUNEL staining is not at all specific for apoptosis. The authors should
also do TUNEL staining at later staining; they will actually see an further increase
in TUNEL positive cells.
- I actually do not understand why the mice gain weight during the first days after
CCL4 injection. Some of the mice almost double their relative liver weight. I
hardly believe that this is the result of liver regeneration. Do the mice loose
weight or do the really again liver weight?
- Why do the KO mice die still die at day 5-9? As shown by the authors liver
injury resolves after 2-3 days following CCL4 challenge and liver regeneration is
obviously not severely impaired in the KO mice.
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
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:9 March 2010
Reviewer: Arndt Vogel
Reviewer's report:
Mann et al. analyzed the role of guanylate cyclase C for CCL4 induced liver
injury in mice . They found that GC-C mice in a mixed background display a
increased mortality following a singly CCL4 injection. This effect was not seen in
mice with a pure C57 background. The work addresses an interesting issue in
principle, but the value of this study in its current form is limited. Overall, the data
provided so far are preliminary. Furthermore the manuscript is very descriptive
the exact mechanisms of the observed effects remain unclear.
Major comments:
- The apoptosis data are so far not very convincing. Personally, I do not think that
CCL4 induces apoptosis at all. The authors need to employ additional assays
such as caspase-3 activity by Western blot, activity assay and
immunohistochemistry to convincingly show that there is apoptosis following
CCL4. TUNEL staining is not at all specific for apoptosis. The authors should
also do TUNEL staining at later staining; they will actually see an further increase
in TUNEL positive cells.
- I actually do not understand why the mice gain weight during the first days after
CCL4 injection. Some of the mice almost double their relative liver weight. I
hardly believe that this is the result of liver regeneration. Do the mice loose
weight or do the really again liver weight?
- Why do the KO mice die still die at day 5-9? As shown by the authors liver
injury resolves after 2-3 days following CCL4 challenge and liver regeneration is
obviously not severely impaired in the KO mice.
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
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