Sa1332 GASTRIC CORPUS MUCOSAL HYPERPLASIA AND NEUROENDOCRINE CELL HYPERPASIA, BUT NOT SPASMOLYTIC POLYPEPTICE-EXPRESSING METAPLASIA, IS PREVENTED BY A GASTRIN-BLOCKER IN H+/K+ ATPASE BETA SUBUNIT DEFICIENT MICE

Proton pump inhibitor use is associated with an increased risk of gastric cancer, which may be mediated by hypergastrinemia. Spasmolytic polypeptide-expression metaplasia (SPEM) has been proposed as a precursor of gastric cancer. We have examined the effects of the gastrin receptor antagonist netazepide (NTZ) or vehicle on the gastric corpus mucosa of H+/K+ATPase beta subunit knockout (KO) and wild-type (WT) mice. The gastric corpus was evaluated by histopathology, immunohistochemistry (IHC), in situ hybridization (ISH) and whole-genome gene expression analysis, focusing on markers of SPEM and neuroendocrine (NE) cells. KO mice had pronounced hypertrophy, intra- and submucosal cysts and extensive expression of SPEM and NE cell markers in the gastric corpus, but not in the antrum. Numerous SPEM-related genes were upregulated in KO mice compared to WT mice. NTZ reduced hypertrophia, cysts, inflammation and NE hyperplasia. However, NTZ neither affected expression of SPEM markers nor of SPEM-related genes. In conclusion, NTZ prevented mucosal hypertrophy, cyst formation and NE cell hyperplasia but did not affect SPEM. The presence of SPEM seems unrelated to the changes caused by hypergastrinemia in this animal model.

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Skeletal effects of the gastrin receptor antagonist netazepide in H+/K+ATPase beta-subunit deficient mice

Bone Abstracts ◽

10.1530/boneabs.3.oc3.6 ◽

2014 ◽

Cited By ~ 1

Author(s):

Kristin Matre Aasarod ◽

Masoud Ramezanzadeh Koldeh ◽

Mats Peder Mosti ◽

Astrid Kamilla Stunes ◽

Bjorn Ivar Viggaklev ◽

...

Keyword(s):

Receptor Antagonist ◽

Beta Subunit ◽

Gastrin Receptor ◽

Skeletal Effects ◽

Deficient Mice

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Decreased bone mineral density and reduced bone quality in H+/K+ATPase beta-subunit deficient mice

Journal of Cellular Biochemistry ◽

10.1002/jcb.23337 ◽

2011 ◽

Vol 113 (1) ◽

pp. 141-147 ◽

Cited By ~ 16

Author(s):

Reidar Fossmark ◽

Astrid K. Stunes ◽

Christiane Petzold ◽

Helge L. Waldum ◽

Marina Rubert ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Quality ◽

Bone Mineral ◽

Beta Subunit ◽

Mineral Density ◽

Deficient Mice

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Comparison of localization of metallothionein in tissues of metallothionein-deficient mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141585 ◽

1995 ◽

Vol 53 ◽

pp. 1042-1043

Author(s):

H. Nishimura ◽

R Nishimura ◽

D.L. Adelson ◽

A.E. Michaelska ◽

K.H.A. Choo ◽

...

Keyword(s):

Metal Binding ◽

Immunohistochemical Staining ◽

Squamous Epithelium ◽

Rabbit Antiserum ◽

Slight Modification ◽

Positive Control ◽

Heavy Metal Binding ◽

Critical Organ ◽

Metal Binding Protein ◽

Deficient Mice

Metallothionein (MT), a cysteine-rich heavy metal binding protein, has several isoforms designated from I to IV. Its major isoforms, I and II, can be induced by heavy metals like cadmium (Cd) and, are present in various organs of man and animals. Rodent testes are a critical organ to Cd and it is still a controversial matter whether MT exists in the testis although it is clear that MT is not induced by Cd in this tissue. MT-IV mRNA was found to localize within tongue squamous epithelium. Whether MT-III is present mainly glial cells or neurons has become a debatable topic. In the present study, we have utilized MT-I and II gene targeted mice and compared MT localization in various tissues from both MT-deficient mice and C57Black/6J mice (C57BL) which were used as an MT-positive control. For MT immunostaining, we have used rabbit antiserum against rat MT-I known to cross-react with mammalian MT-I and II and human MT-III. Immunohistochemical staining was conducted by the method described in the previous paper with a slight modification after the tissues were fixed in HistoChoice and embedded in paraffin.

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