Overview

The PDGFRβ^(S)J conditional knockin allele has the endogenous PDGFRβ sequences replaced with a floxed-STOP cassette upstream of the constitutively active PDGFRβJ mutant isoform (V536A mutation in the juxtamembrane domain). Following Cre recombinase-mediated excision of the floxed-STOP cassette, expression of the constitutively active mutant PDGFRβ leads to high basal kinase activity without the addition of ligand. These mutant mice may be useful in studying PDGFR signaling in multipotent progenitor mural cells (pericytes and vascular smooth muscle cells), as well as in cardiovascular and obesity-related disease.

Donating Investigator

Dr. Philippe Soriano, Mount Sinai School of Medicine

Genetic overview

Genetic Background	Generation

Pdgfrb^{tm13(Pdgfrb)Sor}

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Pdgfrb	platelet derived growth factor receptor, beta polypeptide

View Genetics

Research Applications

Research Tools
Internal/Organ Research
Immunology, Inflammation and Autoimmunity Research
Developmental Biology Research
Hematological Research
Cardiovascular Research
Cell Biology Research
Cancer Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

The PDGFRβ^(S)J conditional knockin allele has the endogenous PDGFRβ sequences replaced with a loxP-flanked PGKneo (lox-stop-lox) cassette upstream of the constitutively active PDGFRβJ mutant isoform (V536A mutation in the juxtamembrane domain disrupts a highly conserved juxtamembrane region in type III receptor tyrosine kinases that contacts the kinase domain important for full auto-inhibition, leading to constitutive PDGFRβ activity). Prior to Cre recombinase exposure, no expression of the constitutively active βJ mutant isoform is observed, and the mutant allele functions as a knockout. Mice homozygous for the PDGFRβ^(S)J allele are neonatal lethal. Heterozygous PDGFRβ^(S)J mice are viable and fertile with no reported abnormalities. Following Cre recombinase-mediated excision of the floxed-STOP cassette, high basal kinase activity without the addition of ligand is observed in the cre-expressing tissues.

Of note, pan-deletion of the floxed-STOP cassette can be achieved by breeding PDGFRβ^(S)J conditional knockin mice with mice expressing Cre recombinase in early embryonic development (Meox2-Cre [Stock No. 003755], Sox2-Cre [Stock No. 004783], or Prm-Cre [Stock No. 003328]). In the resulting double mutant offspring, widespread expression of the constitutively active PDGFRβ leads to normal embryonic development but eventual death by ~14 days of age. In these double mutant mice, constitutively active PDGFRβ induces a battery of immune response genes in pericytes and mesenchymal cells, and also inhibits in vitro differentiation of white adipocytes.

When PDGFRβ^(S)J conditional knockin mice are bred to Sm22-Cre mice [Stock No. 004746], constitutively active PDGFRβ drives cell proliferation and downregulates differentiation genes in aortic vascular smooth muscle tissues of the double mutant offspring.

Importantly, the donating investigator reports they have not observed any consistent phenotypic differences between the Cre recombinase-activated phenotypes of PDGFRβJ and PDGFRβK (see Stock No. 018435) mice, regardless of Cre recombinase tissue specificity.

Development

To create the PDGFRβ^(S)J targeting vector, Dr. Philippe Soriano (Mount Sinai School of Medicine) isolated a full-length mouse platelet derived growth factor β (Pdgfrb) cDNA sequence and introduced a valine to alanine substitution at codon 536 (V536A) of the juxtamembrane domain by site-directed mutagenesis. This βJ mutation results in a constitutively active mutant PDGFRβ. A loxP-flanked PGKneo cassette (lox-stop-lox) was placed between the splice acceptor and the initiating codon of the mutant cDNA sequence. This construct replaced the endogenous Pdgfrb exons 2-4 via electroporation into 129S4/SvJaeSor-derived AK7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and the resulting chimeric males were mated with females to generate the PDGFRβ^(S)J knockin mouse line. Mutant mice were bred to B6;129 mice harboring other mutations/transgenes, and/or to C57BL/6J wildtype, and/or C57BL/6NTac wildtype mice for several generations prior to sending to The Jackson Laboratory Repository. The donating investigator reports selecting PDGFRβ^(S)J mice with no other mutations present for breeding. Upon arrival, mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish The Jackson Laboratory Repository colony.

Control Suggestions

Wild-type from the colony

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Olson LE; Soriano P. 2011. PDGFRbeta Signaling Regulates Mural Cell Plasticity and Inhibits Fat Development. Dev Cell 20(6):815-26PubMed: 21664579 MGI: J:173602

View All References

Genetics

Pdgfrb^{tm13(Pdgfrb)Sor}

Allele Symbol: Pdgfrb^{tm13(Pdgfrb)Sor}

Allele Name	targeted mutation 13, Philippe Soriano
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	targeted mutation 13, Philippe Soriano; Pdgfrb^{tm13(Pdgfrb)Sor}
Gene Symbol and Name	Pdgfrb, platelet derived growth factor receptor, beta polypeptide
Gene Synonym(s)	Pdgfr; AI528809; PDGFR; PDGFR1; PDGFR-1; IMF1; IBGC4; JTK12; expressed sequence AI528809; platelet derived growth factor receptor; CD140B; CD140b; Pdgfr; PENTT; KOGS
Strain of Origin	129S4/SvJaeSor
Chromosome	18
Molecular Note	Exons 2 and 3 were replaced with a splice acceptor, floxed neo/stop cassette, and the mouse cDNA with nucleotide substitution(s) that results in the amino acid substitution of alanine for valine at position 536 (V536A). This mutation is an activating mutation.
Mutations Made By	Dr. Philippe Soriano, Mount Sinai School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Research Tools
- Immunology, Inflammation and Autoimmunity Research
- Genetics Research
  - Mutagenesis and Transgenesis: Cre-lox System
- Cancer Research
  - tumor immunology
- Diabetes and Obesity Research
  - loxP
- Cardiovascular Research
  - Cre-lox System
- Cre-lox System
  - loxP-flanked Sequences
- Developmental Biology Research
  - Cre-lox System
Internal/Organ Research
- Adipose Defects
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules
- Growth Factors/Receptors/Cytokines
Developmental Biology Research
- Mesodermal Defects
- Perinatal Lethality
  - Homozygous
Hematological Research
- Immunological Defects
Cardiovascular Research
- Other
- Heart Abnormalities
Cell Biology Research
- Signal Transduction
Cancer Research
- Growth Factors/Receptors/Cytokines

Mammalian Phenotype Terms by Genotype

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

Genotype: Pdgfrb^{tm13(Pdgfrb)Sor}/Pdgfrb⁺ Meox2^tm1(cre)Sor/Meox2⁺
involves: 129S4/SvJaeSor * C57BL/6

growth/size/body region phenotype

postnatal growth retardation
- during the second week

mortality/aging

postnatal lethality, complete penetrance
- usually by P14

Genotype: Pdgfrb^{tm13(Pdgfrb)Sor}/Pdgfrb⁺ Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
involves: 129S4/SvJae * C57BL/6 * CBA

cardiovascular system phenotype

increased aorta wall thickness
- during the second week, mice exhibit thickening of the ascending aorta media compared with wild-type mice

growth/size/body region phenotype

postnatal growth retardation
- during the second week

mortality/aging

postnatal lethality, complete penetrance
- usually by P14

References

Olson LE; Soriano P. 2011. PDGFRbeta Signaling Regulates Mural Cell Plasticity and Inhibits Fat Development. Dev Cell 20(6):815-26PubMed: 21664579 MGI: J:173602

Additional - Pdgfrb^{tm13(Pdgfrb)Sor} related

Technical Support

Contact Technical Support

Genotyping Protocols
- Pyrosequencing:** Pdgfrb*V536A
- Standard PCR:Pdgfrb^{tm13(Pdgfrb)Sor}
- Separated PCR:Pdgfrb^{tm13(Pdgfrb)Sor}
- Genotyping resources and troubleshooting
Breeding Considerations

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). Homozygous mice die shortly after birth.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Pdgfrb^{tm13(Pdgfrb)Sor}/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018434 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

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or Wildtype for Pdgfrb<tm13(Pdgfrb)Sor>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

Related Products and Services

Frozen Mouse Embryo	STOCK Pdgfrb<tm13(Pdgfrb)Sor>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	STOCK Pdgfrb<tm13(Pdgfrb)Sor>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	STOCK Pdgfrb<tm13(Pdgfrb)Sor>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	STOCK Pdgfrb<tm13(Pdgfrb)Sor>/J Frozen Embryo	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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.

Terms Of Use

Terms of Use

General Terms and Conditions

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

JAX® Mice, Products & Services Conditions of Use

"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"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "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 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, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Pdgfrbtm13(Pdgfrb)Sor

Allele Symbol: Pdgfrbtm13(Pdgfrb)Sor

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Pdgfrbtm13(Pdgfrb)Sor/Pdgfrb+ Meox2tm1(cre)Sor/Meox2+involves: 129S4/SvJaeSor * C57BL/6

growth/size/body region phenotype

mortality/aging

Genotype: Pdgfrbtm13(Pdgfrb)Sor/Pdgfrb+ Edil3Tg(Sox2-cre)1Amc/Edil3+involves: 129S4/SvJae * C57BL/6 * CBA

cardiovascular system phenotype

growth/size/body region phenotype

mortality/aging

References

Additional - Pdgfrbtm13(Pdgfrb)Sor 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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Pdgfrb^{tm13(Pdgfrb)Sor}

Allele Symbol: Pdgfrb^{tm13(Pdgfrb)Sor}

Genotype: Pdgfrb^{tm13(Pdgfrb)Sor}/Pdgfrb⁺ Meox2^tm1(cre)Sor/Meox2⁺
involves: 129S4/SvJaeSor * C57BL/6

Genotype: Pdgfrb^{tm13(Pdgfrb)Sor}/Pdgfrb⁺ Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
involves: 129S4/SvJae * C57BL/6 * CBA

Additional - Pdgfrb^{tm13(Pdgfrb)Sor} related