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

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Research Applications

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

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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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

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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)	PDGFRbeta^(S)J
Gene Symbol and Name	Pdgfrb, platelet derived growth factor receptor, beta polypeptide
Gene Synonym(s)
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 Phenotype

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
- Separated PCR:Pdgfrb
- 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/Product	Description	Price
	Heterozygous or Wildtype for Pdgfrb<tm13(Pdgfrb)Sor>

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

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

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Questions about Terms of Use

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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 Phenotype

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