FVB.Cg-Slc9a2^tm1Ges/Mmjax

Stock number: 013743
Research areas: Cell Biology Research, Research Tools

Description

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.

Detailed description

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.

Development

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. The construct was electroporated into 129-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were bred to Black Swiss females, and these mice were subsequently backcrossed to FVB/N mice for at least 10 generations. Upon arrival at The Jackson Laboratory, mice were bred to FVB/NJ inbred mice for at least one generation to establish the colony.

Allele

Symbol: Slc9a2^tm1Ges
Name: targeted mutation 1, Gary E Shull
MGI accession ID: MGI:2447441
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Slc9a2
Marker name: solute carrier family 9 (sodium/hydrogen exchanger), member 2
Chromosome: 1
Strain of origin: Not Specified
Molecular note: The gene was disrupted by insertion of a neomycin resistance gene into exon 2, which encodes transmembrane domains 2-7 (amino acids 99-252). Northern blot analysis detected reduced levels of mutant transcript in kidney, small and large intestines, and high levels of mutant transcript in stomach of homozygous mutant animals. Sequence analysis revealed a cryptic splice donor site at codon 172 of exon 2 spliced to the acceptor of site exon 3. This alternative transcript results in a frameshift eliminating 614 out of 813 amino acids. The deleted region includes 9 out of 12 putative transmembrane domains and the carboxy terminal hydrophilic domain.