Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Harriet Tenenhouse,   McGill University

Description
Mice that are homozygous for the targeted mutation are viable and fertile, and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern blot analysis of bone, kidney, liver or lung, or by Western blot analysis of kidney. Homozygotes are smaller in size and have reduced weight compared to wildtype littermates. Secondary ossification defects revealed at weaning are followed by compensatory bone development. Mutant mice exhibit increased urinary excretion of inorganic phosphate and calcium, diet dependent hypercalciuria and hypercalcemia, as well as decreased serum parathyroid hormone levels, increased serum alkaline phosphatase activity, and elevated serum 1,25-dihyudroxyvitamin D. Homozygous mice do not respond to dietary challenges of low inorganic phosphate or parathyroid hormone content. Calcium and inorganic phosphate containing renal stones, nephrocalcinosis, are found in homozygotes at all ages. This mutant mouse strain may be useful in studies of hereditary hypophosphatemic rickets with hypercalciuria, HHRH, and familial hypercalciuria.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 6 to 10, encoding amino acids 178-389. The construct was electroporated into 129S2/SvPas derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts.

Control Information

	Control
	000664 C57BL/6J
		C57BL/6J mice (Stock 000664) may be used as controls.
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Hypophosphatemic Rickets with Hypercalciuria, Hereditary; HHRH - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Slc34a1^tm1Hten/Slc34a1^tm1Hten

        involves: 129S2/SvPas * C57BL/6J

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:47637)
  • incomplete penetrance, with 44% dying prior to weaning
  • death attributed to poor nutritional status
• behavior/neurological phenotype
• abnormal eating behavior (MGI Ref ID J:47637)
• lethargy (MGI Ref ID J:47637)
• weakness (MGI Ref ID J:47637)
• growth/size phenotype
• decreased body weight (MGI Ref ID J:47637)
  • significantly reduced at birth
• homeostasis/metabolism phenotype
• abnormal vitamin level (MGI Ref ID J:47637)
  • elevated serum concentration of 1,25-dihydroxy vitamin D
• decreased circulating parathyroid hormone level (MGI Ref ID J:47637)
• hypercalcemia (MGI Ref ID J:47637)
• hypercalciuria (MGI Ref ID J:47637)
• hyperphosphaturia (MGI Ref ID J:47637)
• hypophosphatemia (MGI Ref ID J:47637)
• renal/urinary system phenotype
• hypercalciuria (MGI Ref ID J:47637)
• hyperphosphaturia (MGI Ref ID J:47637)
• skeleton phenotype
• abnormal cancellous bone morphology (MGI Ref ID J:47637)
  • poor initial development of cancellous bone
  • by 45 days of age, the number metaphyseal trabeculae exceeded that in wild-type
• abnormal skeleton development (MGI Ref ID J:47637)
  • initial impairment of secondary ossification in the epiphysis observed at 21 days of age
  • by 45 days of age, the skeletal phenotype had reversed and overcompensated

View Research Applications

Research Applications

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

Slc34a1^tm1Hten related

Cell Biology Research
Channel and Transporter Defects

Endocrine Deficiency Research
Kidney Defects

Internal/Organ Research
Kidney Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Slc34a1tm1Hten
Allele Name		targeted mutation 1, Harriet S Tenenhouse
Allele Type		Targeted (knock-out)
Common Name(s)		NaPi2a-; Npt2-;
Mutation Made By		Harriet Tenenhouse,   McGill University
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Slc34a1, solute carrier family 34 (sodium phosphate), member 1
Chromosome		13
Gene Common Name(s)		NAPI-3; NPT2; NPTIIa; Na/Pi cotransporter; NaPi2A; Npt2; SLC11; SLC17A2; Slc17a2; renal Na+/Pi transporter; sodium phosphate transport 2; solute carrier family 17 (sodium/hydrogen exchanger), member 2;
Molecular Note		Exons 6 through 10 were replaced by a neomycin selection cassette inserted by homologous recombination. The deleted region encoded amino acids 178 through 389. Northern blot and RT-PCR analyses showed reduced levels of transcript in heterozygous mice andand an absence of transcript in homozygous mutant mice. While protein was undetected in homozygous mutant mice by Western blot analysis of renal tissue, normal levels of protein were detected in heterozygotes. [MGI Ref ID J:47637]

Genotyping

Genotyping Information

Genotyping Protocols

Slc34a1^tm1Hten, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Beck L; Karaplis AC; Amizuka N; Hewson AS; Ozawa H; Tenenhouse HS. 1998. Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities. Proc Natl Acad Sci U S A 95(9):5372-7. [PubMed: 9560283]  [MGI Ref ID J:47637]

Additional References

Khadeer MA; Tang Z; Tenenhouse HS; Eiden MV; Murer H; Hernando N; Weinman EJ; Chellaiah MA; Gupta A. 2003. Na+-dependent phosphate transporters in the murine osteoclast: cellular distribution and protein interactions. Am J Physiol Cell Physiol 284(6):C1633-44. [PubMed: 12606316]  [MGI Ref ID J:83898]

Slc34a1^tm1Hten related

Chau H; El-Maadawy S; McKee MD; Tenenhouse HS. 2003. Renal calcification in mice homozygous for the disrupted type IIa Na/Pi cotransporter gene Npt2. J Bone Miner Res 18(4):644-57. [PubMed: 12674325]  [MGI Ref ID J:111272]

Gupta A; Tenenhouse HS; Hoag HM; Wang D; Khadeer MA; Namba N; Feng X; Hruska KA. 2001. Identification of the type II Na(+)-Pi cotransporter (Npt2) in the osteoclast and the skeletal phenotype of Npt2-/- mice. Bone 29(5):467-76. [PubMed: 11704500]  [MGI Ref ID J:109413]

Hoag HM; Martel J; Gauthier C; Tenenhouse HS. 1999. Effects of Npt2 gene ablation and low-phosphate diet on renal Na(+)/phosphate cotransport and cotransporter gene expression. J Clin Invest 104(6):679-86. [PubMed: 10491403]  [MGI Ref ID J:110765]

Khan SR; Glenton PA. 2008. Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter. Am J Physiol Renal Physiol 294(5):F1109-15. [PubMed: 18337544]  [MGI Ref ID J:135986]

Perwad F; Azam N; Zhang MY; Yamashita T; Tenenhouse HS; Portale AA. 2005. Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice. Endocrinology 146(12):5358-64. [PubMed: 16123154]  [MGI Ref ID J:129835]

Sitara D; Razzaque MS; St-Arnaud R; Huang W; Taguchi T; Erben RG; Lanske B. 2006. Genetic ablation of vitamin D activation pathway reverses biochemical and skeletal anomalies in Fgf-23-null animals. Am J Pathol 169(6):2161-70. [PubMed: 17148678]  [MGI Ref ID J:116289]

Tenenhouse HS; Gauthier C; Chau H; St-Arnaud R. 2004. 1alpha-Hydroxylase gene ablation and Pi supplementation inhibit renal calcification in mice homozygous for the disrupted Npt2a gene. Am J Physiol Renal Physiol 286(4):F675-81. [PubMed: 14656762]  [MGI Ref ID J:95432]

Tenenhouse HS; Gauthier C; Martel J; Hoenderop JG; Hartog A; Meyer MH; Meyer RA Jr; Bindels RJ. 2002. Na/P(i) cotransporter ( Npt2) gene disruption increases duodenal calcium absorption and expression of epithelial calcium channels 1 and 2. Pflugers Arch 444(5):670-6. [PubMed: 12194021]  [MGI Ref ID J:106184]

Tenenhouse HS; Martel J; Gauthier C; Segawa H; Miyamoto K. 2003. Differential effects of Npt2a gene ablation and X-linked Hyp mutation on renal expression of Npt2c. Am J Physiol Renal Physiol 285(6):F1271-8. [PubMed: 12952859]  [MGI Ref ID J:87132]

Tenenhouse HS; Martel J; Gauthier C; Zhang MY; Portale AA. 2001. Renal expression of the sodium/phosphate cotransporter gene, Npt2, is not required for regulation of renal 1 alpha-hydroxylase by phosphate. Endocrinology 142(3):1124-9. [PubMed: 11181527]  [MGI Ref ID J:68782]

Zhao N; Tenenhouse HS. 2000. Npt2 gene disruption confers resistance to the inhibitory action of parathyroid hormone on renal sodium-phosphate cotransport. Endocrinology 141(6):2159-65. [PubMed: 10830304]  [MGI Ref ID J:108816]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-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
	000664 C57BL/6J
		C57BL/6J mice (Stock 000664) may be used as controls.
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

See Terms of Use

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.

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General Terms and Conditions

Contact information

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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