These Slc12a2 (or Nkcc1) knockout mice exhibit growth retardation with a 30% incidence of death by the time of weaning. They are deaf, have less body fat, reduced mean arterial blood pressure, exhibit reduced cAMP-induced short circuit currents in jejunum, cecum, and trachea, unusual head postures, and engage in circling behaviors and rapid spinning, but have difficulty maintaining their balance. These mice may be useful for studying the regulation of cell volume, and the control of Cl- and K+ secretion in the maintenance of hearing 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) | Slc12a2 | solute carrier family 12, member 2 |
Homozygotes: A targeting vector was designed to insert a neomycin resistance (neo) cassette into exon 6 of the solute carrier family 12, member 2 (Slc12a2 or Nkcc1) gene, abolishing gene function. Homozygous mice are viable, fertile, and exhibit growth retardation with a 30% incidence of death by the time of weaning. Nkcc1 regulates cell volume and is expressed in vascular endothelial cells where it is required for controlling cytosolic concentrations of Cl- and K+, and in the basolateral membranes of epithelial cells where it provides an entry pathway for ions that are secreted across the apical membrane. These Nkcc1-/- mice are significantly smaller than their wildtype littermates by 1 week of age, and remain 80% smaller as adults. They are deaf, have less body fat, reduced mean arterial blood pressure, and exhibit reduced cAMP-induced short circuit currents in jejunum, cecum, and trachea. These mutant mice also demonstrate unusual head postures, and engage in circling behaviors and rapid spinning, but have difficulty maintaining their balance. The lumen of the cochlear duct of these mice is collapsed, and Reissner's membrane lies against the interdental cells of the spiral limbus, the tectorial membrane, and the stria vascularis. These mice may be useful for studying the regulation of cell volume, and the control of Cl- and K+ secretion in the maintainance of hearing and blood pressure.
Heterozygote: Heterozygous mice are viable, fertile, and normal in size. They exhibit normal growth, and are phenotypically similar to wildtype mice with the exception of slightly reduced blood pressure.
A targeting vector was designed to insert a neomycin resistance (neo) cassette into exon 6 of the solute carrier family 12, member 2 (Slc12a2 or Nkcc1) 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) | Nkcc1- |
Gene Symbol and Name | Slc12a2, solute carrier family 12, member 2 |
Gene Synonym(s) | |
Strain of Origin | 129 |
Chromosome | 18 |
Molecular Note | Insertion of a neomycin gene into exon 6. Northern blot analysis of brain, heart, skeletal muscle, lung, kidney, stomach, small intestine and colon failed to detect any mRNA in homozygous mutants. |
Mutations Made By | Gary Shull, University of Cincinnati |
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to FVB/NJ inbred mice. Homozygous mice are runted and engage in circling behavior and rapid spinning. The donating investigator confirms that 30% of homozygotes die by 4 weeks of age.
When using the FVB.Cg-Slc12a2tm1Ges/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34262 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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