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.
Gary E Shull, University of Cincinnati
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Slc9a2 | solute carrier family 9 (sodium/hydrogen exchanger), member 2 |
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.
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 Name | targeted mutation 1, Gary E Shull |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | NHE2- |
Gene Symbol and Name | Slc9a2, solute carrier family 9 (sodium/hydrogen exchanger), member 2 |
Gene Synonym(s) | |
Strain of Origin | Not Specified |
Chromosome | 1 |
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. |
Mutations Made By | Gary Shull, University of Cincinnati |
When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony, or to FVB/NJ inbred mice. Homozygous matings produce few litters.
When using the FVB.Cg-Slc9a2tm1Ges/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34265 in your Materials and Methods section.
Facility Barrier Level Descriptions
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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