Review for 10.1186/s12876-019-1009-x (2019)

Reviewer ’s report  
 
Title: Histopathological features of the proper gastric glands in FVB/N -background mice 
carrying constitutively -active aryl -hydrocarbon receptor  
 
Version: 0 Date: 30 Oct 2017  
 
Reviewer: Robert Coffey  
 
Reviewer's report:  
 
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The authors report that transgenic mice expressing constitutively -active AhR (CA -AhR) develop 
gastric lesions mimicking gastritis cystica profunda. How ever, this finding has been previously 
reported. The histological findings are more consistent with spasmolytic polypeptide -expressing 
metaplasia (SPEM) than intestinal metaplasia.  
 
Major points  
1. The authors report that CA -AhR induces intramucosal (IM) a nd extramucosal (EM) cysts, 
foveolar hyperplasia, fused gastric pit, decreased number of parietal and chief cells, lymphocytic 
infiltration near the cysts, and downward migration of the proliferation center. All the findings 
were previously reported using a different strain of mice. Only differences are that EM cysts 
develop earlier in the current study using FVB -CA-AhR mice (8 weeks) compared to prior 
studies using B6/CBA -CA-AhR mice (10 weeks) and that EM cysts are confined in the stomach 
in FVB -CA-AhR mi ce, whereas EM cysts develop also in cecum and ileum in B6/CBA -CA-AhR 
mice. Phenotypic differences in different strains have been well -described. The authors are 
encouraged to identify the factors that can explain the phenotypic differences between FVB -CA-
AhR and B6/CBA -CA-AhR.  
2. The authors argue that CA -AhR induces intestinal metaplasia in the stomach solely based on 
alcian blue positivity. However, it is known that deep glandular cells of gastric antrum are 
positive for alcian blue in mice. Intestinal m etaplasia in mice requires both histologic goblet cell 
morphology and immunohistochemical Muc2 - or Tff3 -positivity. In this reviewer's opinion, 
phenotypes of CA -AhR mice resemble SPEM rather than intestinal metaplasia. Immunostaining 
with SPEM markers such  as Tff2 or CD44v9 should be performed.  
 
Minor points  
1. Terms of lamina muscularis and muscular layer are repeatedly used in the manuscript. Correct 
terms are (lamina) muscularis mucosae and muscularis propria.  
2. [Line 259] The manuscript reads that the epithelial cells lining cysts are squamous or 
columnar shaped and refers Fig. 5d. However, Fig. 5d only shows columnar epithelium.  
3. In discussion, the authors say that it would be interesting to study the functional crosstalk 
between AhR activation and L gr5+ stem cells. However, phenotypes of AhR activation is 
confined in the corpus and Lgr5+ stem cells are not present in the corpus but present only in the 
antrum and cardia.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work inc lude the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
  
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