Overview

Also Known As:NHE4^-

These Slc9a4 (or Nhe4) knockout mice exhibit a reduction in gastric acid, reduced numbers of parietal cells, a loss of mature chief cells, increased numbers of mucous and undifferentiated cells, and an increase in the number of necrotic and apoptotic cells. These mice may be useful for studying gastric acid secretion, gastric epithelial cell differentiation, and development of secretory canalicular and tubulovesicular membranes.

Donating Investigator

Gary E Shull, University of Cincinnati

Genetic overview

Genetic Background	Generation

Slc9a4^tm1Ges

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Slc9a4	solute carrier family 9 (sodium/hydrogen exchanger), member 4

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Research Applications

Research Tools
Cell Biology Research

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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 4 (Slc9a4 or Nhe4) gene, abolishing gene function. Homozygous Nhe4^-/- mice are viable, fertile, and normal in size. Nhe4 is expressed on the basolateral membrane of gastric parietal cells and zymogenic (chief) cells, and is required for normal levels of gastric acid secretion, secretory membrane development, and parietal cell and chief cell differentiation. These mutant mice display a reduction in gastric acid and their gastric mucosa contain reduced numbers of parietal cells, a loss of mature chief cells, increased numbers of mucous and undifferentiated cells, and an increase in the number of necrotic and apoptotic cells. In addition, the parietal cells of Nhe4^-/- mice exhibit limited development of canalicular membranes and a virtual absence of tubulovesicles. These mice may be useful for studying gastric acid secretion, gastric epithelial cell differentiation, and development of secretory canalicular and tubulovesicular membranes.

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 4 (Slc9a4 or Nhe4) gene. The construct was electroporated into 129S6/SvEvTac-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting chimeric males were bred to Black Swiss females. Upon arrival at the The Jackson Laboratory, mice were bred to 129S1/SvImJ inbred mice for at least one generation to establish the colony.

Control Suggestions

Approximate Controls

Wild-type from the colony
002448 129S1/SvImJ

Additional Information

Considerations for Choosing Controls

Selected References

Gawenis LR; Greeb JM; Prasad V; Grisham C; Sanford LP; Doetschman T; Andringa A; Miller ML; Shull GE. 2005. Impaired gastric acid secretion in mice with a targeted disruption of the NHE4 Na+/H+ exchanger. J Biol Chem 280(13):12781-9PubMed: 15684419 MGI: J:98566

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Genetics

Slc9a4^tm1Ges

Allele Symbol: Slc9a4^tm1Ges

Allele Name	targeted mutation 1, Gary E Shull
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	NHE4^-
Gene Symbol and Name	Slc9a4, solute carrier family 9 (sodium/hydrogen exchanger), member 4
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	1
Molecular Note	A targeting construct was designed to insert a neomycin resistance into exon 2. Northern blot demonstrated a reduction in the size of the transcript in mutant stomach tissue. Sequence analysis showed that exon 2 and the neo gene had been excised and exon 1 was spliced to exon 3.
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:

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

Mammalian Phenotype Terms by Genotype

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

Genotype: Slc9a4^tm1Ges/Slc9a4^tm1Ges
involves: 129S6/SvEvTac * Black Swiss

cellular phenotype

gastric necrosis

endocrine/exocrine gland phenotype

abnormal gastric parietal cell morphology
- parietal cells are smaller mostly from a decrease in the cytoplasmic compartment and have abnormal secretory canaliculi
- the number of parietal cells appear to be reduced

abnormal mucous neck cell morphology
- the number of mucous cells is increased

abnormal gastric chief cell morphology
- the number of chief cells appear to be reduced

immune system phenotype

stomach inflammation
- some evidence of inflammation including eosinophilic infiltration is seen

mammalian phenotype

growth/size/body region phenotype
- Normal - growth and survival are normal

digestive/alimentary phenotype

abnormal stomach glandular epithelium morphology
- the number of parietal and chief cells appears to be reduced and the number of mucous cells increased, in addition more enteroendocrine and relatively undifferentiated cells are seen
- mucous pit cells often contain intracytoplasmic cystic structures
- glands in the gastric mucosa appear atrophic with increased interglandular space
- parietal cells are smaller mostly from a decrease in the cytoplasmic compartment and have abnormal secretory canaliculi

abnormal stomach mucosa morphology
- a modest increase in the number of apoptotic and necrotic cells is seen; however no ciliated cells were seen in the gastric mucosa

stomach inflammation
- some evidence of inflammation including eosinophilic infiltration is seen

abnormal gastric chief cell morphology
- the number of chief cells appear to be reduced

abnormal gastric parietal cell morphology
- parietal cells are smaller mostly from a decrease in the cytoplasmic compartment and have abnormal secretory canaliculi
- the number of parietal cells appear to be reduced

abnormal mucous neck cell morphology
- the number of mucous cells is increased

gastric necrosis

hypochlorhydria
- the pH of gastric secretions is significantly more alkaline at 18 days, 9 weeks, and 6 months of age but alkalinity does not increase with age

References

Gawenis LR; Greeb JM; Prasad V; Grisham C; Sanford LP; Doetschman T; Andringa A; Miller ML; Shull GE. 2005. Impaired gastric acid secretion in mice with a targeted disruption of the NHE4 Na+/H+ exchanger. J Biol Chem 280(13):12781-9PubMed: 15684419 MGI: J:98566

Additional - Slc9a4^tm1Ges related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Slc9a4
- Separated MCA:Slc9a4
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the NHE4^- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34266 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.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:NHE4-

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Slc9a4tm1Ges

Allele Symbol: Slc9a4tm1Ges

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Slc9a4tm1Ges/Slc9a4tm1Gesinvolves: 129S6/SvEvTac * Black Swiss

cellular phenotype

endocrine/exocrine gland phenotype

immune system phenotype

mammalian phenotype

digestive/alimentary phenotype

References

Additional - Slc9a4tm1Ges 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

Also Known As:NHE4^-

Slc9a4^tm1Ges

Allele Symbol: Slc9a4^tm1Ges

Genotype: Slc9a4^tm1Ges/Slc9a4^tm1Ges
involves: 129S6/SvEvTac * Black Swiss

Additional - Slc9a4^tm1Ges related