In this strain the targeted allele replaces exon 1 of the endogenous mouse solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1 (Slc9a3r1) gene with a neomycin (neo) resistance cassette, abolishing gene function. These mice may be useful for studying renal, gastrointestinal, and hepatic transport.
Edward J Weinman, University of MD, Baltimore
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Slc9a3r1 | solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1 |
In this strain exon 1 of the endogenous mouse solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1 (Slc9a3r1, or Nherf-1) gene is disrupted by a neomycin (neo) resistance cassette, abolishing gene function. No homozygous females are obtained in the first 3 generations of backcrosses. Nherf-1-/- females obtained between F4 and F6 generations have 30-50% reduction in bodyweight over wildtype littermates, show impaired mobility, and some develop hydrocephaly. Most homozygous females die 30-35 days after birth due to reduced bone mineral density. Associated bone fractures are observed. Male homozygotes display an increase in urinary excretion of uric acid, a decrease in serum phosphate concentration, an increase in serum alkaline phosphatase, a 3-fold increase in urinary phosphate excretion, a slight increase in urinary magnesium excretion, but maintain normal overall renal function. Homozygotes also exhibit abnormalities in the targeting and signalling of a number of hormone receptors including the B2-adreneric receptor, the PTH1 receptor, the k-opiod receptor, and dopamine receptors. NHERF-1 heterozygous mice exhibit an intermediate phenotype,are viable, fertile, and normal in size. The donating investigator notes that colonies on a 129/SvJ background only yield 2-3 animals per litter. These mice may be useful for studying renal, gastrointestinal, and hepatic transport.
A targeting vector was designed to replace exon 1 of the solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1 (Slc9a3r1) gene with a neomycin (neo) resistance cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric mice were bred to C57BL/6J mice to generate a colony of Nherf-1-/- mice. These mice were subsequently backcrossed at least 7 generations onto a C57BL/6J background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis performed by The Jackson Laboratory revealed 8 of 32 markers (on four different chromosomes) that were not C57BL/6J allele-type. These data suggest 129S genetic contamination prior to arrival at The Jackson Laboratory.
Allele Name | targeted mutation 1, Shirish Shenolikar |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | NHERF1-; NHERF-1(-); Nherf1- |
Gene Symbol and Name | Slc9a3r1, solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1 |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 11 |
Molecular Note | Exon 1 was replaced by a neomycin selection cassette inserted by homologous recombination. Protein was undetected in homozygous mutant mice by Western blot analysis of kidney extracts and immunostaining of proximal renal tubules. |
Mutations Made By | Shirish Shenolikar, Duke University Medical Center |
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or with C57BL/6J inbred mice (Stock No. 000664). Female homozygotes have 30-50% reduction in bodyweight, show impaired mobility, and die 30-35 days after birth due to reduced bone mineral density which lead to bone fractures.
When using the B6;129-Slc9a3r1tm1Ssl/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012862 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Slc9a3r1<tm1Ssl> |
Frozen Mouse Embryo | B6;129-Slc9a3r1<tm1Ssl>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129-Slc9a3r1<tm1Ssl>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129-Slc9a3r1<tm1Ssl>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6;129-Slc9a3r1<tm1Ssl>/J Frozen Embryo | $3373.50 |
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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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