Strain Name:

B6N.129-Pik3cgtm1Dwu/J

Stock Number:

024587

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Availability:

Under Development - Now Accepting Orders

Estimated Available for Distribution Date: 26-JAN-15
Use Restrictions Apply, see Terms of Use
PI3Kγ deficient mice express GFP in hematopoietic cells, muscle, and the pancreas and may be useful when studying the role of p110γ in inflammation and inflammatory diseases.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   25-MAR-14
Specieslaboratory mouse
GenerationN12+pN1 (02-JUN-14)
Generation Definitions
 
Donating Investigator Dianqing Wu,   Yale University School of Medicine

Description
A green fluorescent protein (GFP) and a neomycin resistance (neo) cassette replaces part of exon 1 and exons 2-3 of the phosphoinositide-3-kinase, catalytic, gamma polypeptide (Pik3cg) gene, abolishing gene expression. PI3Kγ, p110γ, is expressed in hematopoietic cells, muscle, and the pancreas and facilitates the migration of leukocytes, including neutrophils and eosinophils, to the site of inflammation. Homozygous are viable and fertile. GFP is detected in the splenocytes, bone marrow cells, and neutrophils. GFP was detected with flow cytometry in over 90% of Mac1+ cells in the peritoneum, and 82% of CD45R+ and 70% of CD3+ cells from the spleens of PI3Kγ deficient mice. These mice display impaired neutrophil chemotaxis and respiratory burst in response to formyl peptide N-formyl-Met-Leu-Phe (fMLP) and C5a induction, as well as reduced thymocyte survival and activation of mature T lymphocytes. Neutrophils have decreased PIP3 production and AKT activation, and peritoneal macrophages display reduced migration and accumulation in a septic peritonitis model. These PI3Kγ deficient mice exhibit decreased bone reabsorption and an increase in apoptosis during osteoclast differentiation. An increase in IL-17A production in also seen in splenocytes.

Development
A targeting vector was designed to replace part of exon 1 and exons 2-3 of the phosphoinositide-3-kinase, catalytic, gamma polypeptide (Pik3cg) gene with a green fluorescent protein (GFP) and a neomycin resistance (neo). The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6NHsd females. These mice were bred to C57BL/6NHsd for at least 12 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.

Control Information

  Control
   005304 C57BL/6NJ (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Pik3cgtm1Dwu/Pik3cgtm1Dwu

        B6.Cg-Pik3cgtm1Dwu
  • mortality/aging
  • increased sensitivity to induced morbidity/mortality
    • at high viral titers of vaccinia virus, mice exhibit rapid weight loss, become ill, and die within 5 days unlike similarly treated wild-type mice   (MGI Ref ID J:131923)
  • immune system phenotype
  • *normal* immune system phenotype
    • naive CD8+ T cell migration, activation, proliferation, and differentiation are normal   (MGI Ref ID J:131923)
    • abnormal CD8-positive, alpha-beta T cell physiology
      • CD8+ T cell migration in vitro in response to LTB4 and CCL5 is reduced compared with wild-type cells   (MGI Ref ID J:131923)
      • CD8+ T cell impaired migration in response to LTB4 is more severe than for CCL5   (MGI Ref ID J:131923)
      • however, migration in response to CCl21 is normal   (MGI Ref ID J:131923)
    • abnormal response to infection
      • following infection with VV-WR (vaccinia virus- Western Reserve strain), mice exhibit reduced influx of CD8+ T and NK cells into the peritoneum compared to in similarly treated wild-type mice   (MGI Ref ID J:131923)
      • increased susceptibility to viral infection
        • at high viral titers of vaccinia virus, mice exhibit rapid weight loss, become ill, and die within 5 days unlike similarly treated wild-type mice   (MGI Ref ID J:131923)
    • decreased CD8-positive, alpha-beta T cell number
      • fewer resident CD8+ T cells are detected in the peritoneum compared to in wild-type mice   (MGI Ref ID J:131923)
  • homeostasis/metabolism phenotype
  • abnormal blood coagulation
    • following ferric chloride-induced arterial injury, mice fail to form arterial occlusions or form weak occlusions unlike in similarly treated wild-type mice   (MGI Ref ID J:107460)
    • abnormal platelet physiology
      • spreading of platelets on fibrinogen is impaired compared with wild-type cells   (MGI Ref ID J:107460)
      • however, platelet granule secretion is normal   (MGI Ref ID J:107460)
      • decreased platelet aggregation
        • when stimulated with low concentrations of ADP or collagen   (MGI Ref ID J:107460)
  • decreased platelet calcium level
    • thrombin-stimulated calcium mobilization in platelets is 25% less than in similarly treated wild-type cells   (MGI Ref ID J:107460)
  • hematopoietic system phenotype
  • abnormal CD8-positive, alpha-beta T cell physiology
    • CD8+ T cell migration in vitro in response to LTB4 and CCL5 is reduced compared with wild-type cells   (MGI Ref ID J:131923)
    • CD8+ T cell impaired migration in response to LTB4 is more severe than for CCL5   (MGI Ref ID J:131923)
    • however, migration in response to CCl21 is normal   (MGI Ref ID J:131923)
  • abnormal platelet physiology
    • spreading of platelets on fibrinogen is impaired compared with wild-type cells   (MGI Ref ID J:107460)
    • however, platelet granule secretion is normal   (MGI Ref ID J:107460)
    • decreased platelet aggregation
      • when stimulated with low concentrations of ADP or collagen   (MGI Ref ID J:107460)
  • decreased CD8-positive, alpha-beta T cell number
    • fewer resident CD8+ T cells are detected in the peritoneum compared to in wild-type mice   (MGI Ref ID J:131923)
  • decreased platelet calcium level
    • thrombin-stimulated calcium mobilization in platelets is 25% less than in similarly treated wild-type cells   (MGI Ref ID J:107460)
  • growth/size/body phenotype
  • weight loss
    • at high viral titers of vaccinia virus   (MGI Ref ID J:131923)

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

Pik3cgtm1Dwu/Pik3cgtm1Dwu

        Background Not Specified
  • immune system phenotype
  • decreased immunoglobulin level
    • mice treated with NP-Ficoll produce fewer antibodies containing lambda light chain compared with similarly treated wild-type mice   (MGI Ref ID J:60348)
  • impaired neutrophil chemotaxis
    • in response to fMLP (formyl peptide N-formyl-Met-Leu-Phe) or MIP-1alpha (Ccl3), neutrophil migration is impaired in an in vitro migration assay compared with similarly treated wild-type cells   (MGI Ref ID J:60348)
    • in E. coli-induced peritonitis, neutrophil infiltration into the peritoneal cavity is impaired compared to in similarly treated wild-type mice   (MGI Ref ID J:60348)
  • cellular phenotype
  • impaired neutrophil chemotaxis
    • in response to fMLP (formyl peptide N-formyl-Met-Leu-Phe) or MIP-1alpha (Ccl3), neutrophil migration is impaired in an in vitro migration assay compared with similarly treated wild-type cells   (MGI Ref ID J:60348)
    • in E. coli-induced peritonitis, neutrophil infiltration into the peritoneal cavity is impaired compared to in similarly treated wild-type mice   (MGI Ref ID J:60348)
  • hematopoietic system phenotype
  • decreased immunoglobulin level
    • mice treated with NP-Ficoll produce fewer antibodies containing lambda light chain compared with similarly treated wild-type mice   (MGI Ref ID J:60348)
  • impaired neutrophil chemotaxis
    • in response to fMLP (formyl peptide N-formyl-Met-Leu-Phe) or MIP-1alpha (Ccl3), neutrophil migration is impaired in an in vitro migration assay compared with similarly treated wild-type cells   (MGI Ref ID J:60348)
    • in E. coli-induced peritonitis, neutrophil infiltration into the peritoneal cavity is impaired compared to in similarly treated wild-type mice   (MGI Ref ID J:60348)
View Research Applications

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

Apoptosis Research

Cell Biology Research
Cell Motility Defects

Immunology, Inflammation and Autoimmunity Research
Inflammation
      Neutrophil defects

Research Tools
Genetics Research
      Tissue/Cell Markers

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Pik3cgtm1Dwu
Allele Name targeted mutation 1, Dianqing Wu
Allele Type Targeted (Null/Knockout, Reporter)
Common Name(s) PI3Kgamma-; p110gamma-;
Gene Symbol and Name Pik3cg, phosphoinositide-3-kinase, catalytic, gamma polypeptide
Chromosome 12
Gene Common Name(s) 5830428L06Rik; PI(3)Kgamma; PI3CG; PI3K; PI3Kgamma; PI3Kgamma; PIK3; RIKEN cDNA 5830428L06 gene; p110gamma; p120-PI3K;
Molecular Note A part of the first exon and the entire second and third exons were replaced by a GFP gene, which was fused in-frame to the coding sequence of Pik3cg. GFP is expressed under the control of Pik3cg promoter elements in this allele. [MGI Ref ID J:60348]

Genotyping

Genotyping Information

Genotyping Protocols

Pik3cgtm1Dwu, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Li Z; Jiang H; Xie W; Zhang Z; Smrcka AV; Wu D. 2000. Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction [see comments] Science 287(5455):1046-9. [PubMed: 10669417]  [MGI Ref ID J:60348]

Additional References

Pik3cgtm1Dwu related

Bach TL; Chen QM; Kerr WT; Wang Y; Lian L; Choi JK; Wu D; Kazanietz MG; Koretzky GA; Zigmond S; Abrams CS. 2007. Phospholipase cbeta is critical for T cell chemotaxis. J Immunol 179(4):2223-7. [PubMed: 17675482]  [MGI Ref ID J:151225]

Chang JD; Sukhova GK; Libby P; Schvartz E; Lichtenstein AH; Field SJ; Kennedy C; Madhavarapu S; Luo J; Wu D; Cantley LC. 2007. Deletion of the phosphoinositide 3-kinase p110gamma gene attenuates murine atherosclerosis. Proc Natl Acad Sci U S A 104(19):8077-82. [PubMed: 17483449]  [MGI Ref ID J:121582]

Hannigan M; Zhan L; Li Z; Ai Y; Wu D; Huang CK. 2002. Neutrophils lacking phosphoinositide 3-kinase gamma show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis. Proc Natl Acad Sci U S A 99(6):3603-8. [PubMed: 11904423]  [MGI Ref ID J:146418]

Harris SJ; Ciuclan L; Finan PM; Wymann MP; Walker C; Westwick J; Ward SG; Thomas MJ. 2012. Genetic ablation of PI3Kgamma results in defective IL-17RA signalling in T lymphocytes and increased IL-17 levels. Eur J Immunol 42(12):3394-404. [PubMed: 22930133]  [MGI Ref ID J:190357]

Jackson SP; Schoenwaelder SM; Goncalves I; Nesbitt WS; Yap CL; Wright CE; Kenche V; Anderson KE; Dopheide SM; Yuan Y; Sturgeon SA; Prabaharan H; Thompson PE; Smith GD; Shepherd PR; Daniele N; Kulkarni S; Abbott B; Saylik D; Jones C; Lu L; Giuliano S; Hughan SC; Angus JA; Robertson AD; Salem HH. 2005. PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat Med 11(6):507-14. [PubMed: 15834429]  [MGI Ref ID J:98315]

Joo JD; Kim M; Horst P; Kim J; D'Agati VD; Emala CW Sr; Lee HT. 2007. Acute and delayed renal protection against renal ischemia and reperfusion injury with A1 adenosine receptors. Am J Physiol Renal Physiol 293(6):F1847-57. [PubMed: 17928414]  [MGI Ref ID J:127544]

Kang H; Chang W; Hurley M; Vignery A; Wu D. 2010. Important roles of PI3Kgamma in osteoclastogenesis and bone homeostasis. Proc Natl Acad Sci U S A 107(29):12901-6. [PubMed: 20616072]  [MGI Ref ID J:162404]

Li H; Park D; Abdul-Muneer PM; Xu B; Wang H; Xing B; Wu D; Li S. 2013. PI3Kgamma inhibition alleviates symptoms and increases axon number in experimental autoimmune encephalomyelitis mice. Neuroscience 253:89-99. [PubMed: 24012746]  [MGI Ref ID J:207434]

Lian L; Wang Y; Draznin J; Eslin D; Bennett JS; Poncz M; Wu D; Abrams CS. 2005. The relative role of PLCbeta and PI3Kgamma in platelet activation. Blood 106(1):110-7. [PubMed: 15705797]  [MGI Ref ID J:107460]

Martin AL; Schwartz MD; Jameson SC; Shimizu Y. 2008. Selective regulation of CD8 effector T cell migration by the p110gamma isoform of phosphatidylinositol 3-kinase. J Immunol 180(4):2081-8. [PubMed: 18250413]  [MGI Ref ID J:131923]

Nienaber JJ; Tachibana H; Naga Prasad SV; Esposito G; Wu D; Mao L; Rockman HA. 2003. Inhibition of receptor-localized PI3K preserves cardiac beta-adrenergic receptor function and ameliorates pressure overload heart failure. J Clin Invest 112(7):1067-79. [PubMed: 14523044]  [MGI Ref ID J:85806]

Schoenwaelder SM; Ono A; Nesbitt WS; Lim J; Jarman K; Jackson SP. 2010. Phosphoinositide 3-kinase p110 beta regulates integrin alpha IIb beta 3 avidity and the cellular transmission of contractile forces. J Biol Chem 285(4):2886-96. [PubMed: 19940148]  [MGI Ref ID J:159946]

Schoenwaelder SM; Ono A; Sturgeon S; Chan SM; Mangin P; Maxwell MJ; Turnbull S; Mulchandani M; Anderson K; Kauffenstein G; Rewcastle GW; Kendall J; Gachet C; Salem HH; Jackson SP. 2007. Identification of a unique co-operative phosphoinositide 3-kinase signaling mechanism regulating integrin alpha IIb beta 3 adhesive function in platelets. J Biol Chem 282(39):28648-58. [PubMed: 17673465]  [MGI Ref ID J:125348]

Smith DF; Deem TL; Bruce AC; Reutershan J; Wu D; Ley K. 2006. Leukocyte phosphoinositide-3 kinase {gamma} is required for chemokine-induced, sustained adhesion under flow in vivo. J Leukoc Biol 80(6):1491-9. [PubMed: 16997858]  [MGI Ref ID J:116569]

Thomas MS; Mitchell JS; Denucci CC; Martin AL; Shimizu Y. 2008. The p110{gamma} isoform of phosphatidylinositol 3-kinase regulates migration of effector CD4 T lymphocytes into peripheral inflammatory sites. J Leukoc Biol 84(3):814-23. [PubMed: 18523230]  [MGI Ref ID J:138164]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   25-MAR-14

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


 

This strain is currently Under Development - Now Accepting Orders.
Estimated Available for Distribution Date: 26-JAN-15

Please note: You may now place orders for this strain although it is not yet ready for distribution. Estimated available for distribution dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for distribution depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain.

Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHeterozygous for Pik3cgtm1Dwu  
$232.00Female or MaleHomozygous for Pik3cgtm1Dwu  
Price per Pair (US dollars $)Pair Genotype
$464.00Heterozygous for Pik3cgtm1Dwu x Heterozygous for Pik3cgtm1Dwu  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHeterozygous for Pik3cgtm1Dwu  
$301.60Female or MaleHomozygous for Pik3cgtm1Dwu  
Price per Pair (US dollars $)Pair Genotype
$603.20Heterozygous for Pik3cgtm1Dwu x Heterozygous for Pik3cgtm1Dwu  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Control Information

  Control
   005304 C57BL/6NJ (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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.
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