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Hypergastrinemia and hypertrophic gastritis in Hip1r‐deficient mice
Author(s) -
Jain Renu N,
AlMenhali Asma A,
Keeley Theresa M,
Ross Theodora S,
Chew Catherine S,
Samuelson Linda C
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1316-a
Gastrin is a potent growth factor for the gastric mucosa, with hypergastrinemia resulting in increased proliferation of progenitor cells, and increased depth and altered cellular composition of the gastric glands. We report a new mouse model of hypergastrinemia resulting in hypertrophy. Huntingtin‐interacting protein 1 related (Hip1r), which is involved in clathrin‐mediated endocytosis, is abundantly expressed in parietal cells. Hip1r‐deficient mice exhibit parietal cell loss and low acid secretion. They consequently develop hypergastrinemia and a multifaceted cellular transformation of the gastric mucosa, including loss of parietal and chief cells, and marked expansion of an abnormal mucous neck cell lineage. Stomach weight was increased 1.6‐fold, and histological analysis demonstrated increased proliferation with a 2‐fold increase in gland height. These abnormal features are progressive, with metaplastic remodeling of the mucosa occurring as the mice age. Widespread inflammatory infiltrates are associated with the epithelial cell remodeling, including increased expression of interferon gamma. The changes in the corpus foretell cellular transformation events in the antrum, with hyperplasia and eventual antral tumors emerging in older mice. Support: DK56882(LCS) & DK31900 (CSC).