ArticleDisease models & mechanisms2016
A knockin mouse model for human ATP4aR703C mutation identified in familial gastric neuroendocrine tumors recapitulates the premalignant condition of the human disease and suggests new therapeutic strategies.
Article in Disease models & mechanisms, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- The Association Between Proton Pump Inhibitor Use and Gastroenteropancreatic Neuroendocrine Tumors: A Systematic Review.Journal of gastrointestinal cancer · 2025Pooled it
- Intestinal pH: a major driver of human gut microbiota composition and metabolism.Nature reviews. Gastroenterology & hepatology · 2025Review
- Multiple gastric neuroendocrine tumors in a patient with parietal cell dysfunction and adenosine triphosphatase HClinical journal of gastroenterology · 2024Article
- Modeling human gastric cancers in immunocompetent mice.Cancer biology & medicine · 2024Review
- Gastric neuroendocrine neoplasms.Nature reviews. Disease primers · 2024Review
- Preclinical Models of Neuroendocrine Neoplasia.Cancers · 2022Review
- New Developments in Gastric Neuroendocrine Neoplasms.Current oncology reports · 2022Review
- Article
- Case Report: CMV Infection and Same Mechanism-Originated Intestinal Inflammation Compatible With Bowel/Crohn's Disease Is Suggested in ATP4A Mutated-Driven Gastric Neuroendocrine Tumors.Frontiers in medicine · 2021Article
- A genetic origin for acid-base imbalance triggers the mitochondrial damage that explains the autoimmune response and drives to gastric neuroendocrine tumours.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2020Article
- The Altered Metabolic Molecular Signatures Contribute to the RAD001 Resistance in Gastric Neuroendocrine Tumor.Frontiers in oncology · 2020Article
- Exploration of gastric neuroendocrine carcinoma (GNEC) specific signaling pathways involved in chemoresistance via transcriptome andComputational and structural biotechnology journal · 2020Article
- Surgical Mouse Models of Vertical Sleeve Gastrectomy and Roux-en Y Gastric Bypass: a Review.Obesity surgery · 2019Review
- Gastroenteropancreatic neuroendocrine neoplasms: genes, therapies and models.Disease models & mechanisms · 2018Review
- A cumulative effect involving malfunction of the PTH1R and ATP4A genes explains a familial gastric neuroendocrine tumor with hypothyroidism and arthritis.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2017Article
- Insights into gastric neuroendocrine tumors burden.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
By whole exome sequencing, we recently identified a missense mutation (p.R703C) in the human ATP4a gene, which encodes the proton pump responsible for gastric acidification. This mutation causes an aggressive familial type I gastric neuroendocrine tumor in homozygous individuals. Affected individuals show an early onset of the disease, characterized by gastric hypoacidity, hypergastrinemia, iron-deficiency anemia, gastric intestinal metaplasia and, in one case, an associated gastric adenocarcinoma. Total gastrectomy was performed as the definitive treatment in all affected individuals. We now describe the generation and characterization of a knockin mouse model for the ATP4a(R703C) mutation to better understand the tumorigenesis process. Homozygous mice recapitulated most of the phenotypical alterations that were observed in human individuals, strongly suggesting that this mutation is the primary alteration responsible for disease development. Homozygous mice developed premalignant condition with severe hyperplasia, dysplasia and glandular metaplasia in the stomach. Interestingly, gastric acidification in homozygous mice, induced by treatment with 3% HCl acid in the drinking water, prevented (if treated from birth) or partially reverted (if treated during adulthood) the development of glandular metaplasia and dysplasia in the stomach and partially rescued the abnormal biochemical parameters. We therefore suggest that, in this model, achlorhydria contributes to tumorigenesis to a greater extent than hypergastrinemia. Furthermore, our mouse model represents a unique and novel tool for studying the pathologies associated with disturbances in gastric acid secretion.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.