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Histopathological features of the proper gastric glands in FVB/N-background mice carrying constitutively-active aryl-hydrocarbon receptor

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Title: Histopathological features of the proper gastric glands in FVB/N-background mice carrying constitutively-active aryl-hydrocarbon receptor
Authors: Dantsuka, Ai Browse this author
Ichii, Osamu Browse this author →KAKEN DB
Hanberg, Annika Browse this author
Elewa, Yaser Hosny Ali Browse this author
Otsuka-Kanazawa, Saori Browse this author
Nakamura, Teppei Browse this author
Kon, Yasuhiro Browse this author →KAKEN DB
Keywords: Constitutively-active aryl-hydrocarbon receptor
Gastric mucosal abnormality
N mice
Issue Date: 21-Jun-2019
Publisher: BioMed Central
Journal Title: BMC gastroenterology
Volume: 19
Start Page: 102
Publisher DOI: 10.1186/s12876-019-1009-x
PMID: 31226941
Abstract: BackgroundAryl-hydrocarbon receptor (AhR) is a multiple ligand-activated transcription factor that has important roles in xenobiotic, physiological, or pathological functions. Transgenic mice systemically expressing constitutively-active AhR (CA-AhR) have been created to mimic activated AhR signaling in vivo. However, their detailed histopathological features are unclear. In the present study, we generated CA-AhR-expressing FVB/N mice (FVB-CA-AhR mice) and clarified their phenotypes in detail.MethodsMale and female FVB-CA-AhR and wild-type mice were histopathologically examined from 6 to 33weeks of age.ResultsAmong the systemic organs, only the stomachs in FVB-CA-AhR mice showed pathological changes including cystic structures beneath the serosa; in addition, stomach weights increased with age. Histopathologically, cystic structures and alcian blue-positive metaplasia were observed in the mucosa of the proper gastric glands, and these two histometric parameters were positively correlated. Furthermore, proliferating cells shifted from the isthmus to the base of the glands, and parietal cells decreased. Age-related histopathological changes were clearer in females than in males. Importantly, in FVB-CA-AhR mice, intramucosal cysts developed as extramucosal cysts beneath the serosa, penetrating the lamina muscularis mucosae and the muscularis propria. Their incidence reached 100% in 28-week-old male mice and 33-week-old female mice. Extramucosal cysts contained alcian blue-, Griffonia simplicifolia lectin II-, or trefoil factor 2-positive cells, suggesting a stomach origin for the cysts and spasmolytic polypeptide-expressing metaplasia-like lesions.ConclusionsDisease onset occurred earlier in FVB-CA-AhR mice than previously reported in C57BL/6-derived CA-AhR mice. Importantly, the histopathological features were partly similar with gastritis cystica profunda in humans and animals. Excessive activation of AhR signaling aggravated abnormalities in the gastric mucosa and were affected by both genetic- and sex-related factors.
Type: article
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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