Progression of gastric hyperplasia and GCP in <i>Kcne2</i>^−/− mice.

<p>A. Mean stomach weights of <i>Kcne2</i>^+/+ and <i>Kcne2</i>^−/− mice at 3 weeks, 3 months and 12 months.^†significantly different from same genotype at previous time-point, <i>p</i><0.005; * significantly different from <i>Kcne2</i>^+/+ at same time-point, <i>p</i><0.005; one-way ANOVA. B. H&E-stained sections showing normal gastric mucosa from 3-week-old <i>Kcne2</i>^+/+ (<i>left</i>) and <i>Kcne2</i>^−/− (right) mice. Arrows, vacuoles. Scale bar, 200 µm. C. Photomicrograph of H&E-stained sections showing (<i>left</i>) normal gastric mucosa from a 12-month-old <i>Kcne2</i>^+/+ mouse, versus (<i>right</i>) gastritis cystica profunda with three herniated glandular profiles in the submucosa in a <i>Kcne2</i>^−/− littermate. Arrows, vacuoles. *Cysts. Scale bar, 300 µm. D. Higher magnification of vacuolated region from gastric mucosa of 3-week-old <i>Kcne2</i>^−/− mouse from panel B. Arrows, vacuoles. Scale bar, 30 µm. E. Higher magnification of cystic region from gastric mucosa of 1-year-old <i>Kcne2</i>^−/− mouse from panel C. Scale bar, 60 µm.</p

Human parietal cell KCNE2 expression is reduced in gastric carcinomas.

<p>A. Immunofluorescence co-labeling of normal (no disease detected) human gastric glands: KCNQ1 (green) and KCNE2 (red). Arrows: co-localization. Scale bar: 100 µm. B. Immunofluorescence co-labeling of normal (no disease detected) human gastric glands: KCNQ1 (green) and HKA β (red). Arrows: co-localization. Scale bar: 100 µm. C, D. Immunofluorescence co-labeling of human gastric glands from an individual with gastric carcinoma: KCNQ1 (green) and KCNE2 (red). Counterstained with DAPI (blue). Scale bar: 100 µm. Arrows: rare co-localization. Panel D shows an example of complete absence of KCNQ1-KCNE2 co-localization. E. Immunofluorescence co-labeling of human gastric glands from an individual with gastric carcinoma: KCNQ1 (green) and HKA β (red). Counterstained with DAPI (blue). Scale bar: 100 µm. Yellow indicates co-localization. F. Immunofluorescence co-labeling of a human gastric adenocarcinoma: KCNQ1 (green) and KCNE2 (red). Counterstained with DAPI (blue). Scale bar: 400 µm. No KCNQ1-KCNE2 co-localization was observed. G. Immunofluorescence co-labeling of a human gastric adenocarcinoma: KCNQ1 (green) and HKA β (red). Counterstained with DAPI (blue). Scale bar: 100 µm. Yellow indicates co-localization.</p

TFF2-expressing metaplasia in <i>Kcne2</i>^−/− gastric mucosa.

<p>A. <i>Left</i>, Negative control for TFF2 staining in areas of GCP from a <i>Kcne2</i>^−/− mouse, using IgM isotype. Scale bar, 70 µm. <i>Right</i>, TFF2 staining in areas of GCP from a <i>Kcne2</i>^−/− mouse, using IgG isotype. Scale bar, 50 µm. B. TFF2 staining in cystic region of gastric mucosa from a <i>Kcne2</i>^−/− mouse. Scale bar, 50 µm. C. Increased magnification views of TFF2 staining in gastric mucosa from a <i>Kcne2</i>^−/− mouse. <i>Left</i>, gastric gland cross-section; <i>right</i>, gastric gland longitudinal section. Scale bar, 50 µm.</p

Increased gastric Cyclin D1 expression, and neoplasia, in <i>Kcne2</i>^−/− mice.

<p>A. Western blots of lysates from 3 stomachs per genotype from <i>Kcne2</i>^−/− and <i>Kcne2</i>^+/+ mice, using anti-Cyclin D1 (upper) and anti-GAPDH (lower) antibodies. B. Cyclin D1 immunoreactivity at the base of <i>Kcne2</i>^+/+ oxyntic glands (<i>left</i>) versus more widespread, and nuclear, staining in the mucosa of <i>Kcne2</i>^−/− mice (right). Scale bars: 70 µm. C. Higher magnifications of Cyclin D1 immunohistochemistry panels in B. <i>Left</i>, <i>Kcne2</i>^+/+; <i>right</i>, <i>Kcne2</i>^−/−. Scale bars: 40 µm. D. Serosal (<i>left</i>) and mucosal (<i>right</i>) views of 12-month-old <i>Kcne2</i>^+/+ (upper) and <i>Kcne2</i>^−/− (lower) mouse stomachs. <i>Arrows</i>: <i>left panel</i>, cystic changes in the gastric serosa; <i>right panel</i>, pyloric polypoid adenomas extending into the duodenum. E. <i>Left</i>, H&E-stained section showing a thrombus composed of fibrin and glandular epithelium in a thin-walled vessel within the submucosa of a 12-month-old <i>Kcne2</i>^−/− mouse (scale bar, 300 µm). <i>Right</i>, expanded view of thrombus from boxed region in left panel (scale bar, 30 µm). F. CD34 staining of endothelial cells in the thin-walled vessel shown in panel E (brown staining, red arrows). Gray arrow, glandular epithelium. Scale bar, 50 µm. G. An H&E-stained section from the thin-walled vessel in panel F, illustrating the vessel wall (red arrow), and invading glandular epithelium (gray arrow) with region of fibrin adhesion (black arrow). Scale bar, 50 µm. H. Internal control for CD34 staining, showing a blood vessel from the same <i>Kcne2</i>^−/− mouse stomach as in panels E–G, but without glandular epithelial invasion, stained with anti-CD34 antibody (brown staining, red arrow). Scale bar, 50 µm.</p