Overview

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.

Donating Investigator

Gary E Shull, University of Cincinnati

Genetic overview

Genetic Background	Generation

Slc9a2^tm1Ges

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Slc9a2	solute carrier family 9 (sodium/hydrogen exchanger), member 2

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Research Applications

Cell Biology Research
Research Tools

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Details

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.

Control Suggestions

Wild-type from the colony

Approximate Controls

001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

Selected References

Schultheis PJ; Clarke LL; Meneton P; Harline M; Boivin GP; Stemmermann G ; Duffy JJ ; Doetschman T ; Miller ML ; Shull GE. 1998. Targeted disruption of the murine Na+/H+ exchanger isoform 2 gene causes reduced viability of gastric parietal cells and loss of net acid secretion. J Clin Invest 101(6):1243-53PubMed: 9502765 MGI: J:46545

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Genetics

Slc9a2^tm1Ges

Allele Symbol: Slc9a2^tm1Ges

Allele Name	targeted mutation 1, Gary E Shull
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

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Cell Biology Research
- Channel and Transporter Defects
  - sodium/hydrogen
Research Tools
- Apoptosis Research

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Slc9a2^tm1Ges/Slc9a2^tm1Ges
involves: 129X1/SvJ * Black Swiss

digestive/alimentary phenotype

abnormal gastric parietal cell morphology
- parietal cells develop normally but degenerate
- reduced number of gastric parietal cells in the oxyntic mucosa of the gastric corpus

abnormal stomach glandular epithelium morphology
- reduced number of gastric parietal and zymogenic cells in the oxyntic mucosa of the gastric corpus

hypochlorhydria
- reduced acid secretion in adult, but not juvenile, mice

stomach inflammation
- developing around 10 days of age and reaching maximal intensity between 17 and 19 days after birth
- inflammation of the glandular mucosa
- transmural infiltrate first consisting of neutrophils before becoming primarily lymphocytes and plasma cells

immune system phenotype

stomach inflammation
- developing around 10 days of age and reaching maximal intensity between 17 and 19 days after birth
- inflammation of the glandular mucosa
- transmural infiltrate first consisting of neutrophils before becoming primarily lymphocytes and plasma cells

mammalian phenotype

homeostasis/metabolism phenotype
- Normal - blood pH, hydrocarbonate (HCO₃-) and sodium concentrations, and plasma aldosterone levels did not differ from those of wild-type

reproductive system phenotype

abnormal fertility/fecundity
- mating pairs yielded occasional litters but, in general, did not breed well

endocrine/exocrine gland phenotype

abnormal gastric parietal cell morphology
- parietal cells develop normally but degenerate
- reduced number of gastric parietal cells in the oxyntic mucosa of the gastric corpus

References

Schultheis PJ; Clarke LL; Meneton P; Harline M; Boivin GP; Stemmermann G ; Duffy JJ ; Doetschman T ; Miller ML ; Shull GE. 1998. Targeted disruption of the murine Na+/H+ exchanger isoform 2 gene causes reduced viability of gastric parietal cells and loss of net acid secretion. J Clin Invest 101(6):1243-53PubMed: 9502765 MGI: J:46545

Additional - Slc9a2^tm1Ges related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated MCA:Slc9a2
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
When using the FVB.Cg-Slc9a2^tm1Ges/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34265 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

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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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Slc9a2tm1Ges

Allele Symbol: Slc9a2tm1Ges

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Slc9a2tm1Ges/Slc9a2tm1Gesinvolves: 129X1/SvJ * Black Swiss

digestive/alimentary phenotype

immune system phenotype

mammalian phenotype

reproductive system phenotype

endocrine/exocrine gland phenotype

References

Additional - Slc9a2tm1Ges related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Slc9a2^tm1Ges

Allele Symbol: Slc9a2^tm1Ges

Genotype: Slc9a2^tm1Ges/Slc9a2^tm1Ges
involves: 129X1/SvJ * Black Swiss

Additional - Slc9a2^tm1Ges related