These Slc4a2 (or Ae2) knockout mice exhibit postnatal mortality (20%), with all dying by 40 days of age. Mice are emaciated, mildly ataxic, show evidence of dehydration, exhibit hearing loss and defective development of bone, and demonstrate a failure of both molar and incisor tooth eruption.
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) | Slc4a2 | solute carrier family 4 (anion exchanger), member 2 |
Homozygotes: A targeting vector was designed to replace exons 14-17 of the solute carrier family 4 (anion exchanger), member 2 (Slc9a4 or Ae2) gene with a neomycin resistance (neo) cassette, abolishing gene function. 20% of homozygous Ae2-/- mice die postnatally, with all dying by 40 days of age. Ae2 is expressed in epithelial cells of the kidney, respiratory tract, and alimentary tract. Ae2 is required for HCO3- efflux and Cl- influx across the basolateral membrane of gastric parietal cells, which are necessary for normal levels of gastric acid secretion. Ae2-/- mice are emaciated, mildly ataxic, show evidence of dehydration, exhibit hearing loss and defective development of bone, and demonstrate a failure of both molar and incisor tooth eruption.
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 replace exons 14-17 of the solute carrier family 4 (anion exchanger), member 2 (Slc9a4 or Ae2) gene with a neomycin resistance (neo) cassette. 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. This strain was maintained on a 129/Black Swiss background. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ 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) | AE2- |
Gene Symbol and Name | Slc4a2, solute carrier family 4 (anion exchanger), member 2 |
Gene Synonym(s) | |
Strain of Origin | 129S6/SvEvTac |
Chromosome | 5 |
Molecular Note | A neo cassette replaced exons 14-17. Transcripts were expected to utilize the neo polyA, thereby lacking codons 703-1237, which encode the transmembrane domains. Northern blot using probes of sequences 3' to the neo showed that wild-type mRNAs were ablated in mutants, whereas probes of sequences 5' to the neo indicated presence of transcripts consistent in size with two splice variants. An immunofluorescence assay using an antibody that recognizes the C terminus confirmed protein disruption. |
Mutations Made By | Gary Shull, University of Cincinnati |
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony. Homozygous mice have no teeth and 20% die postnatally. All homozygotes die by 40 days of age.
When using the STOCK Slc4a2tm1Ges/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34267 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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