Overview

These floxed Pkd1 (polycystic kidney disease 1 homolog) mutant mice may be useful in generating conditional mutations for studies of polycystic kidney disease.

Donating Investigator

Gregory Germino, Johns Hopkins University School of Medic

Genetic overview

Genetic Background	Generation

Pkd1^tm2Ggg

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Pkd1	polycystin 1, transient receptor poteintial channel interacting

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Research Applications

Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

These mice possess loxP sites on either side of exons 2 through 4 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 2 through 4 deleted in the cre-expressing tissue(s).

For example, when crossed to a strain with widespread Cre recombinase expression (see Stock No. 003553), this mutant mouse strain may be useful in studies of polycystic kidneys.

When bred to mice carrying Gt(ROSA)26Sor^{tm1(cre/ERT)Nat} (Stock No. 004847), tamoxifen-induced Cre-mediated recombination results in increased kidney weight.

Development

A targeting vector containing a FRT-site flanked neo cassette and a loxP site was utilized in the construction of this mutant. This selection cassette was inserted upstream of exon 2 of the targeted gene, and another loxP site was inserted upstream of exon 4. This construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The mice were then crossed to a FLP recombinase expressing strain, on a congenic C57BL/6J background, to remove the selection cassette. Mice that had successfully undergone FLP recombination and no longer retained the cassette but did retain the loxP-flanked exons 2-4 were then backcrossed to C57BL/6 for 12 generations (see SNP note below). Heterozygotes were crossed to generate homozygotes. Upon arrival at The Jackson Laboratory the mice were crossed to C57BL/6J at least once to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, at least 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Piontek KB; Huso DL; Grinberg A; Liu L; Bedja D; Zhao H; Gabrielson K; Qian F; Mei C; Westphal H; Germino GG. 2004. A functional floxed allele of Pkd1 that can be conditionally inactivated in vivo. J Am Soc Nephrol 15(12):3035-43PubMed: 15579506 MGI: J:103719

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Genetics

Pkd1^tm2Ggg

Allele Symbol: Pkd1^tm2Ggg

Allele Name	targeted mutation 2, Gregory G Germino
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Pkd1^cond; Pkd1^flox
Gene Symbol and Name	Pkd1, polycystin 1, transient receptor poteintial channel interacting
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	17
Molecular Note	A neomycin cassette flanked by FRT sites and a single loxP site at the 3' end was inserted into intron 1. Another loxP site was inserted into intron 4 in the same orientation such that exons 2-4 could be removed upon expression of cre recombinase.
Mutations Made By	Gregory Germino, Johns Hopkins University School of Medic

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

polycystic kidney disease 1

Research Areas By Phenotype

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

Research Tools
- Cre-lox System
  - loxP-flanked Sequences

Mammalian Phenotype Terms by Genotype

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

Genotype: Pkd1^tm2Ggg/Pkd1^tm2Ggg Tg(Hoxb7-cre)13Amc/0
involves: 129S4/SvJae * C57BL/6

cellular phenotype

increased kidney cell proliferation
- cell proliferation is increased in kidneys in both early and late stage of cystogenesis

increased kidney apoptosis
- apoptosis is increased in kidneys in P7 and P15 mice

homeostasis/metabolism phenotype

increased blood urea nitrogen level
- BUN levels are increased at P7 and P15

renal/urinary system phenotype

polycystic kidney
- early and late stage of cystogenesis is associated with increased cell proliferation and increased Cux1 expression while late stage cystogenesis is associated with increased apoptosis and increased Cux1 expression
- newborn mice exhibit microscopic kidney cysts derived from both cortical and medullary collecting ducts
- P7 kidneys have more and larger cysts, with less parenchyma compared to those in newborns
- by P15, mice present with huge bilateral masses on their flanks and kidneys are grossly cystic with very little normal renal parenchyma

increased kidney apoptosis
- apoptosis is increased in kidneys in P7 and P15 mice

increased kidney cell proliferation
- cell proliferation is increased in kidneys in both early and late stage of cystogenesis

Genotype: Pkd1^tm2Ggg/Pkd1^tm2Ggg Tg(Pax8-rtTA2SM2)1Koes/0 Tg(tetO-cre)1Jaw/0
involves: 129S4/SvJae C57BL/6 * C57BL6/N * DBA * SJL

growth/size/body region phenotype

increased kidney weight
- mice treated with Dox at P28 for 2 weeks and analyzed at 18 weeks exhibit increased kidney weight/body weight ratio due to cysts
- mice treated with doxycycline (Dox) at P0 and analyzed at P14 exhibit increased kidney weight/body weight ratio due to cysts

homeostasis/metabolism phenotype

increased blood urea nitrogen level
- mice treated with Dox at P28 for 2 weeks show increased blood urea nitrogen levels at 18 weeks of age
- mice treated with Dox at P0 show increased blood urea nitrogen levels at P14

renal/urinary system phenotype

polycystic kidney
- mice treated with Dox at P28 for 2 weeks and analyzed at 18 weeks develop severe cystic kidneys
- mice treated with Dox at P0 and analyzed at P14 exhibit a severe cystic phenotype

increased kidney weight
- mice treated with Dox at P28 for 2 weeks and analyzed at 18 weeks exhibit increased kidney weight/body weight ratio due to cysts
- mice treated with doxycycline (Dox) at P0 and analyzed at P14 exhibit increased kidney weight/body weight ratio due to cysts

Genotype: Pkd1^tm2Ggg/Pkd1^tm2Ggg Tg(MMTV-cre)4Mam/0
involves: 129S4/SvJae * FVB

liver/biliary system phenotype

liver cysts
- 20% exhibit an occasional cyst on the surface of the liver at 10 weeks of age and 100% have multiple hepatic cysts at 20 weeks of age

renal/urinary system phenotype

kidney cysts
- 60% exhibit an occasional cyst on the surface of the kidney at 10 weeks of age and 100% have kidney cysts at 20 weeks of age

Genotype: Pkd1^tm2Ggg/Pkd1⁺ Tg(Pax8-rtTA2SM2)1Koes/0 Tg(tetO-cre)1Jaw/0
involves: 129S4/SvJae C57BL/6 * C57BL6/N * DBA * SJL

mammalian phenotype

renal/urinary system phenotype
- Normal - mice treated with doxycycline (Dox) at P0 and analyzed at P14 do not form kidney cysts

Genotype: Pkd1^tm2Ggg/Pkd1^tm2Ggg Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/Gt(ROSA)26Sor⁺
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

growth/size/body region phenotype

increased kidney weight
- pups from nursing mothers that were injected with tamoxifen to induce Pkd1 deletion in pups, show an increase in the ratio of percent kidney weight to body weight at P23

renal/urinary system phenotype

increased kidney weight
- pups from nursing mothers that were injected with tamoxifen to induce Pkd1 deletion in pups, show an increase in the ratio of percent kidney weight to body weight at P23

References

Piontek KB; Huso DL; Grinberg A; Liu L; Bedja D; Zhao H; Gabrielson K; Qian F; Mei C; Westphal H; Germino GG. 2004. A functional floxed allele of Pkd1 that can be conditionally inactivated in vivo. J Am Soc Nephrol 15(12):3035-43PubMed: 15579506 MGI: J:103719

Additional - Pkd1^tm2Ggg related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Probe:Gt(rosa)26sor Probe
- Standard PCR:Pkd1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129S4-Pkd1^tm2Ggg/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010671 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Pkd1<tm2Ggg>

Related Products and Services

Frozen Mouse Embryo	B6.129S4-Pkd1<tm2Ggg>/J	$2595.00
Frozen Mouse Embryo	B6.129S4-Pkd1<tm2Ggg>/J	$2595.00
Frozen Mouse Embryo	B6.129S4-Pkd1<tm2Ggg>/J	$3373.50
Frozen Mouse Embryo	B6.129S4-Pkd1<tm2Ggg>/J	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

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Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Pkd1tm2Ggg

Allele Symbol: Pkd1tm2Ggg

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Pkd1tm2Ggg/Pkd1tm2Ggg Tg(Hoxb7-cre)13Amc/0involves: 129S4/SvJae * C57BL/6

cellular phenotype

homeostasis/metabolism phenotype

renal/urinary system phenotype

Genotype: Pkd1tm2Ggg/Pkd1tm2Ggg Tg(Pax8-rtTA2S*M2)1Koes/0 Tg(tetO-cre)1Jaw/0involves: 129S4/SvJae * C57BL/6 * C57BL6/N * DBA * SJL

growth/size/body region phenotype

homeostasis/metabolism phenotype

renal/urinary system phenotype

Genotype: Pkd1tm2Ggg/Pkd1tm2Ggg Tg(MMTV-cre)4Mam/0involves: 129S4/SvJae * FVB

liver/biliary system phenotype

renal/urinary system phenotype

Genotype: Pkd1tm2Ggg/Pkd1+ Tg(Pax8-rtTA2S*M2)1Koes/0 Tg(tetO-cre)1Jaw/0involves: 129S4/SvJae * C57BL/6 * C57BL6/N * DBA * SJL

mammalian phenotype

Genotype: Pkd1tm2Ggg/Pkd1tm2Ggg Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

growth/size/body region phenotype

renal/urinary system phenotype

References

Additional - Pkd1tm2Ggg related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Pkd1^tm2Ggg

Allele Symbol: Pkd1^tm2Ggg

Genotype: Pkd1^tm2Ggg/Pkd1^tm2Ggg Tg(Hoxb7-cre)13Amc/0
involves: 129S4/SvJae * C57BL/6

Genotype: Pkd1^tm2Ggg/Pkd1^tm2Ggg Tg(Pax8-rtTA2SM2)1Koes/0 Tg(tetO-cre)1Jaw/0
involves: 129S4/SvJae C57BL/6 * C57BL6/N * DBA * SJL

Genotype: Pkd1^tm2Ggg/Pkd1^tm2Ggg Tg(MMTV-cre)4Mam/0
involves: 129S4/SvJae * FVB

Genotype: Pkd1^tm2Ggg/Pkd1⁺ Tg(Pax8-rtTA2SM2)1Koes/0 Tg(tetO-cre)1Jaw/0
involves: 129S4/SvJae C57BL/6 * C57BL6/N * DBA * SJL

Genotype: Pkd1^tm2Ggg/Pkd1^tm2Ggg Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/Gt(ROSA)26Sor⁺
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

Additional - Pkd1^tm2Ggg related