Homozygotes: A targeting vector was designed to insert a neomycin resistance (neo) cassette into exon 2 of the solute carrier family 9 (sodium/hydrogen exchanger), member 2 (Slc9a2 or Nhe2) gene, abolishing gene function. Homozygous Nhe2-/- mice are viable and normal in size, yet they produced few litters. NHE2 is expressed in gastric epithelia mucous, zymogenic, and parietal cells, as well as the in small intestine, colon, and kidney. In these mutant mice, blood pH, HCO3-, Na+ concentrations and plasma aldosterone levels are identical to wild-type levels, while net acid secretion is reduced just before weaning and is abolished in adult animals. The number of parietal and zymogenic cells of the gastric corpus are reduced. As such, parietal cells are seen in various stages of degeneration; necrotic and dead parietal cells are observed was well as some actively secreting acid, while others are immature or vacuolated. The few mature parietal cells found are filled with an increased quantity of canalicular membranes; mature zymogenic cells are rare. Mucosal thickness on the greater curvature of the stomach is decreased, the stomachs are enlarged and weigh more than in wildtype, and the lamina propria is thickened and contained numerous inflammatory cells. Nhe2-/- mice also exhibit increased Juxtaglomerular Apparatus (JGA) and renal renin content, and increased intrarenal and plasma renin activities. These mice may be useful for studying acid secretion, parietal cell viability, mucosal protection, and regulation of renal salt, water conservation, and blood pressure.

Heterozygote: Heterozygous mice are viable, fertile, and normal in size. They exhibit normal growth and are phenotypically similar to wildtype mice.

These Slc9a2 knockout mice exhibit reduced numbers of parietal and zymogenic cells of the gastric corpus,reduced/ absent net acid secretion, decreased mucosal thickness on the greater curvature of the stomach, enlarged stomach, thickened lamina propria, increased Juxtaglomerular Apparatus (JGA) and renal renin content, and increased intrarenal and plasma renin activities. These mice may be useful for studying acid secretion, parietal cell viability, mucosal protection, and regulation of renal salt, water conservation, and blood pressure.

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