Gast

..We examined the effects of these 2 forms of gastrin on acid secretion in gastrin-deficient mice...

..These findings show that IPF1 is needed for the formation of the pancreas and suggest that it acts to determine the fate of common pancreatic precursor cells and/or to regulate their propagation...

..Here we report the effect of long-term dietary iron modification on gastrin-deficient (Gas(-/-)) and hypergastrinemic cholecystokinin receptor 2-deficient (Cck2r(-/-)) mice, both of which have reduced basal ..

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..Moreover parietal cell atrophy, a known pre-neoplastic lesion, correlates with loss of Shh processing...

..In conclusion, our data reveal partially redundant roles for HNF-6 and OC-2 in developing pancreas and identify new markers for antero-posterior patterning of the gut and for enteroendocrine differentiation...

..TFF2 protein expression in the gastric fundus was elevated in hypergastrinemic (INS-GAS) transgenic mice and reduced in gastrin-deficient mice...

..G-InsKi mice provide a novel animal model for elucidating direct effects of insulin on liver functions...

..Our results suggest that an upregulation of the CCK response system and 5-HT(1A)R in the hypothalamus of Tg/Tg mice may mediate the alterations in the observed behaviors of these mice...

..Study of these mice helps our understanding of how dysregulation of gastrin secretion may be implicated in human disease...

..The discovery of a relationship between iron status and circulating gastrin concentrations opens a new perspective on the mechanisms of iron homeostasis...

Hypergastrinemia in INS-GAS mice leads to accelerated carcinogenesis of the stomach, but the mechanisms have not been well defined...

..We therefore investigated the effects of gastrin on intestinal regeneration following a range of stimuli...

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..Furthermore, this separate linkage group is likely to reside in a chromosomal region of inversion polymorphism between P. maniculatus and P. polionotus...

..2 both in the CNS and in the gut. Transient Nkx6.2 expression was also detected in the developing pancreas. However, analysis of Nkx6.2(-/-) mice did not display any obvious aberrations of pancreatic or stomach development...

..Hence, the aim of this study was to evaluate changes in the acid-secreting parietal cell in gastrin-deficient (GAS-KO) mice...

..Hypergastrinemic mice [mice with mutated gastrin under the control of the beta-actin promoter (ACT-GAS mice)] received the COX-2 inhibitor celecoxib (0, 200, or 500 mg/kg of diet) from 5 wk of age and were killed at 16 ..

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..Here, we addressed whether 1) Gpr40 is expressed in the intestine and 2) Ipf1/Pdx1 function is required for Gpr40 expression...

..Taken together, these studies demonstrate that Hip1r plays a significant role in gastric physiology, mucosal architecture, and secretory membrane dynamics in parietal cells...

..g. metabolic syndrome and hypertension. We hypothesised that adverse outcomes from diabetic pregnancies may be linked to compromised placental function, and sought to identify cellular and molecular abnormalities in diabetic placenta...

..These results indicate that miRNAs are required for proper digestive tract organogenesis and that miR-7a and miR-203 control expression of the stomach homeotic regulator Barx1...

..Although hormones have been associated with cancer risk, the mechanisms have not been determined. The peptide hormone gastrin exerts a suppressive effect on antral gastric carcinogenesis...

..This transgenic mouse provides a useful tool to study the regulation of mouse gastrin gene in vivo, thus contributing to our understanding of the mechanisms involved in transcriptional control of the gastrin gene...

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..Our data help unravel the role of enteroendocrine cells and hormones in lipid absorption and maintenance of the intestinal epithelium...

..However, gastrin-deficient (GAS-KO) mice on a mixed C57BL/6/129Sv genetic background maintained in conventional housing were reported to develop ..

..Our studies suggest a novel possibility that activation of beta-catenin, downstream to the IKKalpha,beta/NFkappaB pathway, may be integral to the hyperproliferative effects of progastrin on proximal colonic crypts...

..This study evaluated the effects of gastrin messenger RNA (mRNA) down-regulation on growth of human pancreatic cancer...

..Nevertheless, histamine is not required for emergence of SPEM following acute oxyntic atrophy...

..2 functions in immature endocrine cells to control NE differentiation in normal intestine and is expressed in most NE tumors of the gut, and is therefore a novel target of diagnosis for patients with gastrointestinal NE tumors...

We previously showed that antral gastric tumors develop in gastrin-deficient (Gas(-/-)) mice. Therefore Gas(-/-) mice were studied sequentially over 12 months to identify molecular mechanisms underlying gastric transformation...

..004) with an increased transferrin saturation. Our data indicate that, in juvenile animals when iron demand is high, circulating gastrin concentrations may alter iron status by a CCK2R-independent mechanism...

..We identified stomach-restricted expression of the forkhead transcription factor FOXQ1...

..Ultrastructural analysis suggests that the gastric acid secretion defect in Foxq1-deficient mice might be due to impairment in the fusion of cytoplasmic tubulovesicles to the apical membrane of secretory canaliculi...

..In the embryo, Notch activation perturbs morphogenesis, possibly through effects on stem or progenitor cells...

..Both gastrin and combined gastrin-CCK deficiency reduced the gastric IAPP and PYY expression...

..Gastrin is known to have stimulatory effects on gastric mucosa; however, long-term effect of gastrin stimulation is not well known...

..Thus these findings suggest that gastrin directly stimulates the growth of the pit cell lineage by inducing its own receptor in pit cell precursors...

..The continuous rapid renewal of these cells makes the intestinal epithelium a model system for the study of stem cell regeneration and lineage commitment...

..Hypergastrinemia occurs frequently in association with acid suppression and Helicobacter infection, but its role in the progression to gastric atrophy and gastric cancer has not been well defined...

..This themes article highlights recent progress in our understanding of the biology of gastrin through studies in genetically modified mice...

..These findings suggest that orexin A may be relevant in the growth and maturation of the gastrointestinal tract during intrauterine life...

..A duplication corresponding to one of these two deficiencies was able to rescue its haplolethality...

..The results show that gastrin is critically important for the function of the acid secretory system...

..Hence, the increase of glycine-extended gastrin in combination with normal levels of carboxyamidated gastrin suggests that G-cells may have another biosynthetic pathway for gastrin...

..These results clearly demonstrated that the G protein-coupled CCK-B/gastrin receptor is essential for the physiological as well as pathological proliferation of gastric mucosal cells in vivo...

..This transgenic study suggests that islet neogenesis can be reactivated in the ductular epithelium of the adult pancreas by local expression of two growth factors, gastrin and TGF alpha...

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..The effect of hypergastrinaemia on tumour growth was reversed by use of antiserum directed against the CCK-2 receptor. Hyper-gastrinaemia may promote proliferation of human colonic adenomas that express CCK-2 receptor isoforms...

..Parietal cells were found to be significantly smaller in the mutant cell preparations, suggesting that gastrin stimulation modulates parietal cell morphology...

..Additionally, a clear role for inflammation was established involving both polymorphonuclear and mononuclear cells in these models, and a link was found between mucosal hypertrophy and increased interleukin-11 (IL-11) expression...

The authors recently reported that gastrin gene knockout (GAS-KO) mice had an increased risk for colon carcinogenesis in response to azoxymethane (AOM) compared with their wild type (WT) littermates...

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..Moreover, neoplastic transformation of the antral gastric mucosa does not require gastrin...

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..These findings are likely to be of relevance to other gastric inflammatory conditions...

..It is concluded that the acidic duodenal pH in CF contributes to the stress on the exocrine pancreas and that normalizing duodenal pH reduces this stress...

..Transfection studies demonstrated that the murine gastrin gene expression is stimulated by epidermal growth factor to the same extent as the human gastrin gene...

..pylori infection results to impaired parietal-cell function (acid hyposecretion), hypergastrinemia and hyperplasia of ECL cells in wild-type mice but leads to vagally induced hypersecretion in gastrin-deficient mice...

..The cis-acting element mediating gastrin responsiveness was mapped to the -69 to -58 region of the HB-EGF promoter. Gastrin stimulation was PKC dependent and at least partially mediated by activation of the EGF receptor...

..The availability of mice with defined regions of segmental haploidy will allow their use in genetic screens and enable accurate models of human 'chromosomal' diseases to be generated...

..To our knowledge, these studies demonstrate for the first time that G-Gly's contribute to colonic mucosal proliferation in vivo...

..These data suggest a role of gastrin in the brain in modulating dopamine release in areas involved in PPI...

..Accordingly, gastrin-deficient (GAS-KO) mice have a severe impairment in acid secretion...

..These results reveal a role for distal cis-regulatory elements in achieving the correct level of extra-pancreatic Pdx1 expression, which is necessary for the production of duodenal GIP cells and stomach gastrin cells...

..Our approach can be extended to any region of the mouse genome...

..The identification of gastrin as a functionally relevant downstream target of the beta-catenin signaling pathway provides a new target for therapeutic modalities in the treatment of colorectal cancer...

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..These results define a transcriptional and signaling pathway of inductive cell interactions in vertebrate organogenesis...

..10-30 days after BrdU injection in mice in which the gastrin gene had been deleted by homologous recombination (Gas-KO) and wild-type (C57BL/6) mice. The time course of labeling was similar in the two groups...

..The region described is one of the targets of a large effort to create a series of mice with regional deletions on mouse chromosome 11 (33-80 cM) that can subsequently be subjected to further mutagenesis...

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..TFF2 is suppressed by the tumor suppressor gene p53, and we will also attempt to show that it is an important downstream target of this tumor suppressor through its activity in regulating the immune system. ..

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..We will test the hypothesis that inhibition of NF-kB in epithelial cell will promote apoptosis and BMDC engraftment. ..

..Overall, these studies will provide new insights into the regulation of HDC gene expression and enzymatic activity, and its function in the gastric mucosa. ..

..Overall, these studies will attempt to define the role of progastrin-derived peptides in stem cell regulation and in bridging genetic pathways in colorectal cancer. ..

..We will test the hypothesis that inhibition of NF-kB in epithelial cell will promote apoptosis and BMDC engraftment. ..

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..We will test the hypothesis that inhibition of NF-kB in epithelial cell will promote apoptosis and BMDC engraftment. ..

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..elements mediating gastrin responsiveness in the HDC gene have been identified as two novel cis-acting elements (GAS-RE1 and GAS-RE2) which are located in tandem downstream of the transcriptional start site, and bind to 52 kD and 35 ..

..b) Elucidate whether over-expression of incompletely processed forms of gastrin stimulate colonic proliferation and predispose mice to colonic carcinoma. c) Evaluate the role of gastrin in gastrointestinal tract development. ..

..felis models. Overall, these studies will utilize gastric cancer models to explore the function and regulation of SP, and may provide further insight into the biology of mucous neck cells. ..

..Our group has developed a hypergastrinemic transgenic (insulin-gastrin or INS-GAS) mouse model that shows progression over time to gastric atrophy, intestinal metaplasia, dysplasia and gastric ..