Ablation of parietal cells is associated with ECL-cell hyperplasia in transgenic mice with a genetically engineered ablation of their parietal cell lineage

2001 ◽  
Vol 120 (5) ◽  
pp. A301-A301
Author(s):  
D CHEN ◽  
C ZHAO ◽  
S FALKMER ◽  
H WALDUM ◽  
J SYDER ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Parietal Cell ◽  
Cell Lineage ◽  
Genetically Engineered ◽  
Parietal Cells ◽  
Cell Hyperplasia ◽  
Ecl Cell

Gastric epithelial morphogenesis in normal and transgenic mice

1997 ◽  
Vol 272 (5) ◽  
pp. G1209-G1220 ◽  
Author(s):  
S. M. Karam ◽  
Q. Li ◽  
J. I. Gordon
Keyword(s):  
Parietal Cell ◽  
Cell Lineage ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Parietal Cells ◽  
Cellular Migration ◽  
Multipotent Stem Cells ◽  
Proliferative Zone ◽  
Beta Subunit Gene

The epithelium located in the corpus of the adult mouse stomach forms mucosal invaginations known as gastric units. Gastric units are populated by members of the pit, parietal, and neck-zymogenic cell lineages all of which are derived from multipotent stem cells. Gastric unit morphogenesis was examined in normal embryonic day 18 (E18) to postnatal day 28 (P28) FVB/N mice with electron microscopy and multilabel immunohistochemistry. E18 units appear as short, solid infoldings (primordial buds), 92% of whose cells represent pit, parietal, and neck cell precursors. Although the total number of cells per bud does not change from P1 to P7, immature cells decrease to 22% as differentiated pit, neck, and parietal cells appear. From P7 to P15, lineage precursors and their differentiated progeny increase and buds elongate. Between P15 and P21 the multipotent stem cell and its descendants are assembled into a distinct proliferative zone (isthmus) located in the midportion of each unit, and cellular migration-differentiation programs become compartmentalized. To examine the role of parietal cells in regulating gastric unit morphogenesis, nucleotides -1035 to +24 of the mouse H(+)-K(+)-adenosinetriphosphatase beta-subunit gene were used to express simian virus 40 large T antigen (SV40 TAg) exclusively in this lineage. SV40 TAg amplified the normally rare pre-parietal cell and disclosed a pre-parietal cell precursor. Pre-parietal cells and their precursors were the predominant cells in E18-P1 transgenic buds. At later stages of development (P1-P28) there was a block in differentiation of pre-parietal to mature parietal cells, a decrease in neck cells, and a marked depletion of zymogenic cells. These findings suggest that members of the parietal cell lineage are the source of instructions that affect the neck-zymogenic cell lineage, even before the gastric unit is compartmentalized into its anatomically distinct pit, isthmus, neck, and base regions.

Sa1346 HYPERGASTRINEMIA DUE TO P-CAB (AN EXTREMELY POTENT GASTRIC ACID SECRETION SUPPRESSOR) USE CAUSE SEVERELY PARIETAL CELL PROTRUSION AND ECL CELL HYPERPLASIA.

2020 ◽  
Vol 158 (6) ◽  
pp. S-325
Author(s):  
Takuji Yamasaki ◽  
Yoshihiro Akita ◽  
Haruna Miyashita ◽  
Ryosuke Miyazaki ◽  
Yuki Maruyama ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Parietal Cell ◽  
Cell Hyperplasia ◽  
Cell Protrusion ◽  
Ecl Cell

Parietal cell hyperstimulation and autoimmune gastritis in cholera toxin transgenic mice

2006 ◽  
Vol 290 (5) ◽  
pp. G970-G979 ◽  
Author(s):  
Lymari Lopez-Diaz ◽  
Karen L. Hinkle ◽  
Renu N. Jain ◽  
Yana Zavros ◽  
Cynthia S. Brunkan ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Acid Secretion ◽  
Cholera Toxin ◽  
Parietal Cell ◽  
Acid Content ◽  
Parietal Cells ◽  
Autoimmune Gastritis ◽  
Camp Signaling ◽  
Parietal Cell Antibodies ◽  
Transgenic Lines

The stimulation of gastric acid secretion from parietal cells involves both intracellular calcium and cAMP signaling. To understand the effect of increased cAMP on parietal cell function, we engineered transgenic mice expressing cholera toxin (Ctox), an irreversible stimulator of adenylate cyclase. The parietal cell-specific H+,K+-ATPase β-subunit promoter was used to drive expression of the cholera toxin A1 subunit (CtoxA1). Transgenic lines were established and tested for Ctox expression, acid content, plasma gastrin, tissue morphology, and cellular composition of the gastric mucosa. Four lines were generated, with Ctox-7 expressing ∼50-fold higher Ctox than the other lines. Enhanced cAMP signaling in parietal cells was confirmed by observation of hyperphosphorylation of the protein kinase A-regulated proteins LASP-1 and CREB. Basal acid content was elevated and circulating gastrin was reduced in Ctox transgenic lines. Analysis of gastric morphology revealed a progressive cellular transformation in Ctox-7. Expanded patches of mucous neck cells were observed as early as 3 mo of age, and by 15 mo, extensive mucous cell metaplasia was observed in parallel with almost complete loss of parietal and chief cells. Detection of anti-parietal cell antibodies, inflammatory cell infiltrates, and increased expression of the Th1 cytokine IFN-γ in Ctox-7 mice suggested that autoimmune destruction of the tissue caused atrophic gastritis. Thus constitutively high parietal cell cAMP results in high acid secretion and a compensatory reduction in circulating gastrin. High Ctox in parietal cells can also induce progressive changes in the cellular architecture of the gastric glands, corresponding to the development of anti-parietal cell antibodies and autoimmune gastritis.

scholarly journals DIPG-41. DISSECTING THE MECHANISTIC BASIS FOR ACVR1 AND PIK3CA MUTATION CO-OCCURRENCE IN DIFFUSE MIDLINE GLIOMAS USING GENETICALLY ENGINEERED MOUSE MODELS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii295-iii295
Author(s):  
Annette Wu ◽  
Tak Mak ◽  
Jerome Fortin
Keyword(s):  
Mouse Models ◽  
Pik3ca Mutation ◽  
Cell Lineage ◽  
Gene Expression Signature ◽  
Genetically Engineered ◽  
Genetically Engineered Mouse Models ◽  
Dismal Prognosis ◽  
Human Pathology ◽  
Genes Encoding ◽  
Mechanistic Basis

Abstract Diffuse midline gliomas (DMGs) are aggressive childhood brain tumors with a dismal prognosis. Most of these tumors carry K27M mutations in histone H3-encoding genes, particularly H3F3A and HIST1H3B. In addition, activating mutations in ACVR1 and PIK3CA co-occur in a subset of DMGs. To understand how these lesions drive the development of DMGs, we generated genetically engineered mouse models in which Acvr1G328V, Hist1h3bK27M, and Pik3caH1047R are targeted to the OLIG2-expressing cell lineage. Animals carrying Acvr1G328V and Pik3caH1047R, with (“AHPO”) or without (“APO”) Hist1h3bK27M, developed high-grade diffuse gliomas involving midline and forebrain regions. Neither Acvr1G328V nor Pik3caH1047R drove tumorigenesis by themselves, but Acvr1G328V was sufficient to cause oligodendroglial differentiation arrest, pointing to a role in the earliest stages of gliomas formation. Transcriptomic analyses of AHPO and APO tumors indicated a predominantly proneural and oligodendrocyte precursor-like gene expression signature, consistent with the corresponding human pathology. Genes encoding transcription factors (TFs) with dual roles in controlling glial and neuronal differentiation were upregulated in tumors. Some of these genes were mildly induced by Acvr1G328V alone. Functional experiments using CRISPR/Cas9-mediated gene editing in patient-derived cell lines confirmed a role for some of these TFs in controlling DMG cell fitness. Overall, our results suggest that Pik3caH1047R consolidates Acvr1G328V-induced glial differentiation arrest to drive DMG development and progression.

Transitional Cell Hyperplasia and Carcinomas in Urinary Bladders of Transgenic Mice with Keratin 5 Promoter-Driven Cyclooxygenase-2 Overexpression

2005 ◽  
Vol 65 (5) ◽  
pp. 1808-1813 ◽  
Author(s):  
Russell D. Klein ◽  
Carolyn S. Van Pelt ◽  
Anita L. Sabichi ◽  
Jorge dela Cerda ◽  
Susan M. Fischer ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Transitional Cell ◽  
Cyclooxygenase 2 ◽  
Cell Hyperplasia ◽  
Keratin 5

Global expression analysis of ECL cells in Mastomys natalensis gastric mucosa identifies alterations in the AP-1 pathway induced by gastrin-mediated transformation

2004 ◽  
Vol 20 (1) ◽  
pp. 131-142 ◽  
Author(s):  
M. Kidd ◽  
T. Hinoue ◽  
G. Eick ◽  
K. D. Lye ◽  
S. M. Mane ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Mucosa ◽  
Western Blot ◽  
Cell Transformation ◽  
Mastomys Natalensis ◽  
Rt Pcr ◽  
Cell Hyperplasia ◽  
Ecl Cells ◽  
Ecl Cell ◽  
Gene Expression Alterations

Enterochromaffin-like (ECL) cell hyperplasia and then irreversible neoplasia can be generated in the African rodent Mastomys natalensis using the H2 receptor blocker, loxtidine, for 8–16 wk. We used a GeneChip approach complemented by standard technologies to identify gene expression alterations in the gastric mucosa during gastrin-mediated ECL cell transformation. Gastric mucosa (mucosal scrapping) and ECL cell-enriched fractions were obtained from untreated Mastomys (controls) and from animals treated with loxtidine for 8 wk (hyperplasia). Tumor ECL cells were obtained by hand-dissection of gastric ECL cell nodules from animals treated with loxtidine for >16 wk and from a spontaneously developed ECL cell tumor. RNA was isolated, examined on rat U34A GeneChips, and comparison analysis was performed to identify altered gene expression. Alterations in gene expressions were examined further by immunohistochemistry, quantitative RT-PCR (Q-RT-PCR), sequencing and Western blot. GeneSpring analysis demonstrated alterations in few genes (<20) in hyperplastic and tumor mucosa. The histamine H1 receptor was consistently increased in proliferating mucosa. This gene change was confirmed by Q-RT-PCR. Other genes showing alterations included neural-(chromogranin A and somatostatin), cell-cycle-, and AP-1-associated genes. Immunostaining confirmed alterations in neural markers. Cluster analysis of ECL cell-enriched samples demonstrated that c- fos and junD were differently regulated. Q-RT-PCR and Western blot in prospectively collected gastric mucosal samples confirmed the differential expression of Fos and Jun. The negative regulators of AP-1, JunD, and Menin were decreased in tumor mucosa. A missense of unknown function was noted in the menin gene. Hypergastrinemia in an animal model of gastric carcinoids differentially altered the histamine type 1 receptor and gene expression and protein composition of AP-1. These results suggest that expression of this receptor and an altered composition of AP-1 with a loss of inhibition play a role in ECL cell transformation.

scholarly journals Transgenic mice: beyond the knockout

2011 ◽  
Vol 300 (2) ◽  
pp. F291-F300 ◽  
Author(s):  
R. Lance Miller
Keyword(s):  
Transgenic Mice ◽  
Fluorescent Proteins ◽  
Primary Cultures ◽  
Cell Lineage ◽  
Tissue Imaging ◽  
Cell Type ◽  
Deep Tissue ◽  
Pure Cell ◽  
Deep Tissue Imaging ◽  
Tremendous Impact

Transgenic mice have had a tremendous impact on biomedical research. Most researchers are familiar with transgenic mice that carry Cre recombinase (Cre) and how they are used to create conditional knockouts. However, some researchers are less familiar with many of the other types of transgenic mice and their applications. For example, transgenic mice can be used to study biochemical and molecular pathways in primary cultures and cell suspensions derived from transgenic mice, cell-cell interactions using multiple fluorescent proteins in the same mouse, and the cell cycle in real time and in the whole animal, and they can be used to perform deep tissue imaging in the whole animal, follow cell lineage during development and disease, and isolate large quantities of a pure cell type directly from organs. These novel transgenic mice and their applications provide the means for studying of molecular and biochemical events in the whole animal that was previously limited to cell cultures. In conclusion, transgenic mice are not just for generating knockouts.

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