Strain Name:

B6;129-Slc9a3r1tm1Ssl/J

Stock Number:

012862

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
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.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.129-Slc9a3r1tm1Ssl/J    (Changed: 22-SEP-11 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
GenerationN8+F1pN1
Generation Definitions
 
Donating Investigator Edward J Weinman,   University of MD, Baltimore

Description
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.

Development
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.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Nephrolithiasis/Osteoporosis, Hypophosphatemic, 2; NPHLOP2   (SLC9A3R1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Slc9a3r1tm1Ssl/Slc9a3r1tm1Ssl

        involves: 129X1/SvJ
  • reproductive system phenotype
  • decreased litter size   (MGI Ref ID J:78606)
  • reduced fertility   (MGI Ref ID J:78606)

Slc9a3r1tm1Ssl/Slc9a3r1tm1Ssl

        involves: 129X1/SvJ * C57BL/6
  • mortality/aging
  • partial prenatal lethality
    • homozygous females were not obtained in generations F1 to F3, but were obtained in generations F4 to F6   (MGI Ref ID J:78606)
  • premature death
    • surviving females died 30 to 35 days after birth, often exhibiting bone fractures   (MGI Ref ID J:78606)
  • behavior/neurological phenotype
  • abnormal locomotor behavior
    • female mice exhibited impaired mobility consistent with muscle weakness   (MGI Ref ID J:78606)
  • homeostasis/metabolism phenotype
  • increased urine phosphate level   (MGI Ref ID J:78606)
  • renal/urinary system phenotype
  • increased urine phosphate level   (MGI Ref ID J:78606)
  • reproductive system phenotype
  • decreased litter size
    • crosses involving homozygous females yielded small litters   (MGI Ref ID J:78606)
  • skeleton phenotype
  • decreased bone mineral content
    • mineral content reduced 40%   (MGI Ref ID J:78606)
  • decreased bone mineral density
    • bone mineral density reduced 25% to 30%   (MGI Ref ID J:78606)
  • nervous system phenotype
  • hydroencephaly
    • observed in some female mice   (MGI Ref ID J:78606)

Slc9a3r1tm1Ssl/Slc9a3r1tm1Ssl

        FVB.129-Slc9a3r1tm1Ssl
  • reproductive system phenotype
  • *normal* reproductive system phenotype
    • contrary to previous reports mice do not exhibit any decreased fertility   (MGI Ref ID J:128912)
  • homeostasis/metabolism phenotype
  • abnormal physiological response to xenobiotic
    • when activated with forskolin, cAMP- and cGMP-activated CFTR transepithelial short circuit currents are decrease 34% compared to wild-type mice   (MGI Ref ID J:128912)
    • when activated with 8-Br-cGMP, cAMP- and cGMP-activated CFTR transepithelial short circuit currents are decrease 31% compared to wild-type mice   (MGI Ref ID J:128912)
    • when activated with forskolin or 8-Br-cGMP, bicarbonate secretion from the duodenum are decreased 35% and 30%, respectively, compared to in wild-type mcie   (MGI Ref ID J:128912)
View Research Applications

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

Endocrine Deficiency Research
Bone/Bone Marrow Defects
      osteopetrosis
Kidney Defects

Internal/Organ Research
Kidney Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Slc9a3r1tm1Ssl
Allele Name targeted mutation 1, Shirish Shenolikar
Allele Type Targeted (Null/Knockout)
Common Name(s) NHERF-1(-); NHERF1-; Nherf1-;
Mutation Made By Shirish Shenolikar,   Duke University Medical Center
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Slc9a3r1, solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1
Chromosome 11
Gene Common Name(s) EBP-50; EBP50; NHE-RF; NHERF; NHERF-1; NHERF1; NPHLOP2; sodium-hydrogen exchanger regulatory factor;
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. [MGI Ref ID J:78606]

Genotyping

Genotyping Information

Genotyping Protocols

Slc9a3r1tm1Ssl, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Slc9a3r1tm1Ssl related

Broere N; Hillesheim J; Tuo B; Jorna H; Houtsmuller AB; Shenolikar S; Weinman EJ; Donowitz M; Seidler U; de Jonge HR; Hogema BM. 2007. Cystic Fibrosis Transmembrane Conductance Regulator Activation Is Reduced in the Small Intestine of Na+/H+ Exchanger 3 Regulatory Factor 1 (NHERF-1)- but Not NHERF-2-deficient Mice. J Biol Chem 282(52):37575-84. [PubMed: 17947234]  [MGI Ref ID J:128912]

Capuano P; Bacic D; Roos M; Gisler SM; Stange G; Biber J; Kaissling B; Weinman EJ; Shenolikar S; Wagner CA; Murer H. 2007. Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient mice. Am J Physiol Cell Physiol 292(2):C927-34. [PubMed: 16987995]  [MGI Ref ID J:119876]

Cunningham R; E X; Steplock D; Shenolikar S; Weinman EJ. 2005. Defective PTH regulation of sodium-dependent phosphate transport in NHERF-1-/- renal proximal tubule cells and wild-type cells adapted to low-phosphate media. Am J Physiol Renal Physiol 289(4):F933-8. [PubMed: 15942053]  [MGI Ref ID J:101246]

Cunningham R; Esmaili A; Brown E; Biswas RS; Murtazina R; Donowitz M; Dijkman HB; van der Vlag J; Hogema BM; De Jonge HR; Shenolikar S; Wade JB; Weinman EJ. 2008. Urine electrolyte, mineral, and protein excretion in NHERF-2 and NHERF-1 null mice. Am J Physiol Renal Physiol 294(4):F1001-7. [PubMed: 18256311]  [MGI Ref ID J:133526]

Cunningham R; Steplock D; Wang F; Huang H; E X; Shenolikar S; Weinman EJ. 2004. Defective parathyroid hormone regulation of NHE3 activity and phosphate adaptation in cultured NHERF-1-/- renal proximal tubule cells. J Biol Chem 279(36):37815-21. [PubMed: 15218020]  [MGI Ref ID J:92569]

Donowitz M; Singh S; Singh P; Salahuddin FF; Chen Y; Chakraborty M; Murtazina R; Gucek M; Cole RN; Zachos NC; Kovbasnjuk O; Broere N; Smalley-Freed WG; Reynolds AB; Hubbard AL; Seidler U; Weinman E; de Jonge HR; Hogema BM; Li X. 2010. Alterations in the proteome of the NHERF1 knockout mouse jejunal brush border membrane vesicles. Physiol Genomics 42A(3):200-10. [PubMed: 20736413]  [MGI Ref ID J:168359]

Giral H; Cranston D; Lanzano L; Caldas Y; Sutherland E; Rachelson J; Dobrinskikh E; Weinman EJ; Doctor RB; Gratton E; Levi M. 2012. NHE3 regulatory factor 1 (NHERF1) modulates intestinal sodium-dependent phosphate transporter (NaPi-2b) expression in apical microvilli. J Biol Chem 287(42):35047-56. [PubMed: 22904329]  [MGI Ref ID J:191894]

Leslie KL; Song GJ; Barrick S; Wehbi VL; Vilardaga JP; Bauer PM; Bisello A. 2013. Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) and nuclear factor-kappaB (NF-kappaB): a feed-forward loop for systemic and vascular inflammation. J Biol Chem 288(51):36426-36. [PubMed: 24196963]  [MGI Ref ID J:207196]

Li M; Wang W; Soroka CJ; Mennone A; Harry K; Weinman EJ; Boyer JL. 2010. NHERF-1 binds to Mrp2 and regulates hepatic Mrp2 expression and function. J Biol Chem 285(25):19299-307. [PubMed: 20404332]  [MGI Ref ID J:164550]

Liu L; Alonso V; Guo L; Tourkova I; Henderson SE; Almarza AJ; Friedman PA; Blair HC. 2012. Na+/H+ exchanger regulatory factor 1 (NHERF1) directly regulates osteogenesis. J Biol Chem 287(52):43312-21. [PubMed: 23109343]  [MGI Ref ID J:193763]

Malmberg EK; Pelaseyed T; Petersson AC; Seidler UE; De Jonge H; Riordan JR; Hansson GC. 2008. The C-terminus of the transmembrane mucin MUC17 binds to the scaffold protein PDZK1 that stably localizes it to the enterocyte apical membrane in the small intestine. Biochem J 410(2):283-9. [PubMed: 17990980]  [MGI Ref ID J:131611]

Murtazina R; Kovbasnjuk O; Zachos NC; Li X; Chen Y; Hubbard A; Hogema BM; Steplock D; Seidler U; Hoque KM; Tse CM; De Jonge HR; Weinman EJ; Donowitz M. 2007. Tissue-specific regulation of sodium/proton exchanger isoform 3 activity in Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) null mice. cAMP inhibition is differentially dependent on NHERF1 and exchange protein directly activated by cAMP in ileum versusproximal tubule. J Biol Chem 282(34):25141-51. [PubMed: 17580307]  [MGI Ref ID J:124705]

Shenolikar S; Voltz JW; Minkoff CM; Wade JB; Weinman EJ. 2002. Targeted disruption of the mouse NHERF-1 gene promotes internalization of proximal tubule sodium-phosphate cotransporter type IIa and renal phosphate wasting. Proc Natl Acad Sci U S A 99(17):11470-5. [PubMed: 12169661]  [MGI Ref ID J:78606]

Song GJ; Barrick S; Leslie KL; Bauer PM; Alonso V; Friedman PA; Fiaschi-Taesch NM; Bisello A. 2012. The scaffolding protein EBP50 promotes vascular smooth muscle cell proliferation and neointima formation by regulating Skp2 and p21(cip1). Arterioscler Thromb Vasc Biol 32(1):33-41. [PubMed: 22034511]  [MGI Ref ID J:195976]

Song GJ; Leslie KL; Barrick S; Bougoin S; Taboas JM; Bisello A. 2012. EBP50 promotes focal adhesion turnover and vascular smooth muscle cells migration. J Mol Cell Cardiol 53(6):809-19. [PubMed: 22974528]  [MGI Ref ID J:192759]

Weinman EJ; Biswas R; Steplock D; Douglass TS; Cunningham R; Shenolikar S. 2010. Sodium-hydrogen exchanger regulatory factor 1 (NHERF-1) transduces signals that mediate dopamine inhibition of sodium-phosphate co-transport in mouse kidney. J Biol Chem 285(18):13454-60. [PubMed: 20200151]  [MGI Ref ID J:162594]

Weinman EJ; Boddeti A; Cunningham R; Akom M; Wang F; Wang Y; Liu J; Steplock D; Shenolikar S; Wade JB. 2003. NHERF-1 is required for renal adaptation to a low-phosphate diet. Am J Physiol Renal Physiol 285(6):F1225-32. [PubMed: 12952857]  [MGI Ref ID J:113637]

Weinman EJ; Mohanlal V; Stoycheff N; Wang F; Steplock D; Shenolikar S; Cunningham R. 2006. Longitudinal study of urinary excretion of phosphate, calcium, and uric acid in mutant NHERF-1 null mice. Am J Physiol Renal Physiol 290(4):F838-43. [PubMed: 16249272]  [MGI Ref ID J:115757]

Weinman EJ; Steplock D; Shenolikar S. 2003. NHERF-1 uniquely transduces the cAMP signals that inhibit sodium-hydrogen exchange in mouse renal apical membranes. FEBS Lett 536(1-3):141-4. [PubMed: 12586353]  [MGI Ref ID J:119442]

Wheeler DS; Barrick SR; Grubisha MJ; Brufsky AM; Friedman PA; Romero G. 2011. Direct interaction between NHERF1 and Frizzled regulates beta-catenin signaling. Oncogene 30(1):32-42. [PubMed: 20802536]  [MGI Ref ID J:170222]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen 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.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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.
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"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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