Strain Name:

C57BL/6J-Aqp2F204V/J

Stock Number:

005921

Availability:

Repository-Cryopreserved

Use Restrictions Apply, see Purchasing Information

Description

Strain Information

Former Names C57BL/6J-Aqp2ndi/J    (Changed: 22-MAR-06 )
Type Chemically Induced Mutation; Coisogenic; Mutant Strain;
Specieslaboratory mouse
 
Donating Investigator Nicholas Gekakis,   Genomics Inst of the Novartis Res Fndtn

Description
Mice homozygous for this mutation are viable with normal body size and lifespan. Homozygotes are fertile, but females usually die during labor. The predicted valine for phenylalanine substitution at amino acid 204 of the mutant protein (F204V) leads to an enrichment in kidney cells of a normally short-lived, intermediately glycosylated 31 kDa isoform and to a reduction in the mature, glycosylated protein level. The mutant AQP2F204V protein is mis-localized in kidney collecting duct cells, and fails to translocate to the apical cell surface in response to desmopressin. Homozygous mice exhibit excessive water consumption and urination, normal plasma glucose levels, and no glucose in the urine. Mutant mice are unable to concentrate urine and exhibit severe hydronephrosis. The presence of some mature, glycosylated protein and a defective, but not completely absent, desmopressin response in homozygous mutant mice likely permits their survival. Heterozygous mice are viable and fertile, and their kidneys appear normal by immunohistochemical analysis. This strain may be useful in studies of diabetes insipidus, kidney metabolism, or intracellular protein translocation, and represents the first published mouse model of nephrogenic diabetes insipidus to survive past the first week of life.

Development
Following multidose ethylnitrosourea (ENU) treatments to induce mutations in founder C57BL/6J mice, a forward genetic screen was utilized to identify offspring for abnormal whole body metabolism. This screening identified a family of mice that urinated and drank excessively. The disorder in these mice segregated in a monogenic, autosomal recessive manner. Sequencing of the endogenous gene coding region of affected mice identified a thymine to guanine (T to G) transversion. This leads to a valine for phenylalanine substitution at amino acid 204 of the protein (F204V).

Control Information

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

Related Strains

Strains carrying other alleles of Aqp2
006881   B6.Cg-Tg(Aqp2-cre)1Dek/J
000530   C57BL/6J-Aqp2cph/J
View Strains carrying other alleles of Aqp2     (2 strains)

Phenotype

Phenotype Information

Related Disease (OMIM) Terms

Diabetes Insipidus, Nephrogenic, Autosomal

Mammalian Phenotype Terms assigned by genotype

Aqp2F204V/Aqp2F204V

        C57BL/6-Aqp2F204V
  • life span-post-weaning/aging
  • *normal* life span-post-weaning/aging (MGI Ref ID J:105809)
    • mutants appear to have normal lifespans, unlike Aqp2 null mice
  • homeostasis/metabolism phenotype
  • decreased urine osmolality (MGI Ref ID J:105809)
    • mice produce very dilute urine; concentration is approximately 161 mOsm compared to about 1,293 mOsm in wild-type
  • behavior/neurological phenotype
  • polydipsia (MGI Ref ID J:105809)
    • water consumption is dramatically higher than in heterozygotes or wild-type
  • renal/urinary system phenotype
  • abnormal kidney physiology (MGI Ref ID J:105809)
    • treatment with 1-deamino-8-D-arginine vasopressin produces a proportionally smaller increase in urine osmolarity compared to wild-type
    • polyuria (MGI Ref ID J:105809)
      • mice have dramatically increased urine output, producing more than their body weight in urine in 24 hours
  • decreased urine osmolality (MGI Ref ID J:105809)
    • mice produce very dilute urine; concentration is approximately 161 mOsm compared to about 1,293 mOsm in wild-type
  • hydronephrosis (MGI Ref ID J:105809)
    • mice exhibit severe hydronephrosis that is detectable at 4 weeks of age and worsens with age
    • ureter morphology is normal despite dilation of the renal pelvis

Research Applications

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

Cell Biology Research
Channel and Transporter Defects

Developmental Biology Research
Internal/Organ Defects (hydronephrosis)
Internal/Organ Defects (kidney)

Internal/Organ Research
Kidney Defects (diabetes insipidus)

Genes & Alleles

Gene & Allele Information

Allele Symbol Aqp2F204V
Allele Name Phe204Val
Common Name(s) Aqp2ndi;
Mutation Made By Nicholas Gekakis,   Genomics Inst of the Novartis Res Fndtn
Strain of OriginC57BL/6
Gene Symbol and Name Aqp2, aquaporin 2
Chromosome 15
Gene Common Name(s) AQP-2; AQP-CD; MGC156502; MGC34501; WCH-CD; aquaporin-2; congenital progressive hydronephrosis; cph; jpk; juvenile polycystic kidneys;
Molecular Note A T to G transversion in the coding region of the gene led to a valine to phenylalanine substitution at postion 204 of the protein. The mutant protein was distributed randomly throughout collecting duct cells of the kidney rather than localized to the subapical region of collecting duct cells in the wild-type kidney. [MGI Ref ID J:105809]

Genotyping

Genotyping Information

Genotyping Protocols

Aqp2F204V, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Lloyd DJ; Hall FW; Tarantino LM; Gekakis N. 2005. Diabetes Insipidus in Mice with a Mutation in Aquaporin-2. PLoS Genet 1(2):e20. [PubMed: 16121255]  [MGI Ref ID J:105809]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are bred as heterozygotes. Homozygous mice are fertile, but females almost always die during labor. Homozygous mice exhibit excessive water consumption and urination.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations             View   International   Pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
Cryopreserved Embryos Fee $1600.00
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryopreserved Embryos
    This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page.
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

Pricing for International shipping destinations             View   USA, Canada and Mexico   Pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
Cryopreserved Embryos Fee $2080.00
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryopreserved Embryos
    This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page.
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
  International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

View JAX® Mice & Services Conditions of Use.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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.
Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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