Strain Name:

STOCK Pik3r1tm1Lca/J

Stock Number:

012871

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Cryopreserved - Ready for recovery

These p85αloxP mice harbor loxP sites flanking exon 7 (the first common exon for the three encoded isoforms [p85α, p55α, and p50α]) of the phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) locus. These mutant mice may be useful in generating conditional mutations for studying class IA phosphoinositide 3-kinases (PI3Ks) in cell growth, cell proliferation cell survival signaling, insulin signaling and tumor angiogenesis, as well as genomic aberrations that promote tumorigenesis/cancer through upregulation of the PI3K/AKT signaling axis.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
GenerationF?+N1F3pN1
Generation Definitions
 
Donating Investigator Lewis C Cantley,   Beth Israel Deaconess Medical Center

Description
Mice homozygous for this p85αloxP allele are viable and fertile, with loxP sites flanking exon 7 of the targeted gene. The Pik3r1 locus encodes three proteins (p85α, p55α, and p50α) that arise from alternative transcription initiation sites; and exon 7 is the first common exon for all three isoforms. When bred to mice that express Cre recombinase, the resulting offspring will have exon 7 deleted in the cre-expressing tissue(s); splicing of upstream exons (exon 6, 1b, or 1c) directly into the downstream exon 8 results in a frameshift mutation that introduces an immediate stop codon. Such a deletion should prevent the translation of the SH2 and p110-binding domains, eliminating the ability to form a functional protein from any of the three transcription initiation sites. These mutant mice may be useful in generating conditional mutations for studying class IA phosphoinositide 3-kinases (PI3Ks) in cell growth, cell proliferation cell survival signaling, insulin signaling and tumor angiogenesis, as well as genomic aberrations that promote tumorigenesis/cancer through upregulation of the PI3K/AKT signaling axis.

When these p85αloxP mice are bred with p85β mutant mice (Stock No. 012872) and Tie2-Cre transgenic mice (Stock No. 004128), the resulting multiple mutant mice may be used to study vascular integrity during development and tumor neovascularization/angiogenesis.

When these p85αloxP mice are bred with p85β mutant mice (Stock No. 012872) and MCK-Cre transgenic mice (Stock Nos. 006405 or 006475), the resulting multiple mutant mice may be used to study protection from cardiac hypertrophy.

Development
The Pik3r1 locus encodes three proteins (p85α, p55α, and p50α) that arise from alternative transcription initiation sites; and all three transcripts share the last nine exons (exons 7-15). A targeting vector was designed to insert an frt-flanked PGK-neo cassette and a loxP site upstream of exon 7, and a second loxP site downstream of exon 7 of the targeted locus. The donating investigator reports that the construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells, and chimeric mice were bred with C57BL/6NCrl mice to generate the colony. At some point, mutant mice were bred with Flp recombinase-expressing mice (Rosa26-FLP on undisclosed genetic background; see Stock No. 003946) to remove the frt-flanked neo cassette. The resulting p85αloxP mice (with single frt site remaining upstream of the floxed exon 7) were bred together to remove the Rosa26-FLP allele. p85αloxP mice on a mixed genetic background (C57BL/6, 129Sv, FVB/N, and maybe others) were sent to The Jackson Laboratory Repository (see additional information below). Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the p85αloxP colony.

Prior to arrival at The Jackson Laboratory Repository, p85αloxP mice were also bred with Cre recombinase-expressing mice, conditional EGFP-expressing mice, and Pik3r2 mutant mice (Stock No. 012872); this results in the mixed genetic background (C57BL/6, 129Sv, FVB/N, and maybe others). The donating investigator reports that the mice did not harbor Cre recombinase when they were sent to The Jackson Laboratory Repository. Colony managers here at The Jackson Laboratory Repository will assay the mice (and selectively breed away any unwanted mutant alleles, if necessary) to maintain the p85αloxP colony.

Control Information

  Control
   101043 B6129SF1/J (approximate)
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Agammaglobulinemia 7, Autosomal Recessive; AGM7   (PIK3R1)
Immunodeficiency 36; IMD36   (PIK3R1)
SHORT Syndrome   (PIK3R1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Pik3r1tm1Lca/Pik3r1tm1Lca Tg(Ckmm-cre)5Khn/0

        involves: 129S6/SvEvTac * C57BL/6 * FVB   (conditional)
  • normal phenotype
  • no abnormal phenotype detected
    • mutants are viable and fertile, with no gross abnormalities and normal muscle morphology   (MGI Ref ID J:102176)
View Research Applications

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

Cancer Research
Genes Regulating Growth and Proliferation
Growth Factors/Receptors/Cytokines
Other

Cell Biology Research
Cell Cycle Regulation
Genes Regulating Growth and Proliferation
Signal Transduction
Transcriptional Regulation

Diabetes and Obesity Research
Insulin Receptors and Growth Factors

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines
Intracellular Signaling Molecules

Research Tools
Cancer Research
Cell Biology Research
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Genetics Research
      Mutagenesis and Transgenesis: Cre-lox System
Reproductive Biology Research
      Cre-lox System

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Pik3r1tm1Lca
Allele Name targeted mutation 1, Lewis C Cantley
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) P85alphaloxP; Pik3r1flox; pik3r1loxP;
Mutation Made By Lewis Cantley,   Beth Israel Deaconess Medical Center
Strain of Origin129S6/SvEvTac
Gene Symbol and Name Pik3r1, phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha)
Chromosome 13
Gene Common Name(s) AA414921; AGM7; GRB1; IMD36; PI3K; PI3KA; expressed sequence AA414921; p50alpha; p55alpha; p85; p85-ALPHA; p85alpha;
Molecular Note A targeting vector was designed such that exon 7 is flanked by loxP sequences. Upon cre-mediated deletion of the exon, splicing of upstream exons 6, 1b or 1c directly into exon 8 results in a frameshift mutation producing an immediate stop codon. As a result the p85alpha isoform is truncated and p55alpha and p50alpha are essentially abolished. Flp mediated recombination removed the neo cassette. Western blot demonstrates the floxed allele is expressed just like the wild-type. [MGI Ref ID J:102176]

Genotyping

Genotyping Information

Genotyping Protocols

Pik3r1tm1Lca, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Luo J; McMullen JR; Sobkiw CL; Zhang L; Dorfman AL; Sherwood MC; Logsdon MN; Horner JW; DePinho RA; Izumo S; Cantley LC. 2005. Class IA phosphoinositide 3-kinase regulates heart size and physiological cardiac hypertrophy. Mol Cell Biol 25(21):9491-502. [PubMed: 16227599]  [MGI Ref ID J:102176]

Yuan TL; Choi HS; Matsui A; Benes C; Lifshits E; Luo J; Frangioni JV; Cantley LC. 2008. Class 1A PI3K regulates vessel integrity during development and tumorigenesis. Proc Natl Acad Sci U S A 105(28):9739-44. [PubMed: 18621722]  [MGI Ref ID J:137878]

Additional References

Pik3r1tm1Lca related

Acosta-Martinez M; Luo J; Elias C; Wolfe A; Levine JE. 2009. Male-biased effects of gonadotropin-releasing hormone neuron-specific deletion of the phosphoinositide 3-kinase regulatory subunit p85alpha on the reproductive axis. Endocrinology 150(9):4203-12. [PubMed: 19541766]  [MGI Ref ID J:157340]

Chen S; Burgin S; McDaniel A; Li X; Yuan J; Chen M; Khalaf W; Clapp DW; Yang FC. 2010. Nf1-/- Schwann cell-conditioned medium modulates mast cell degranulation by c-Kit-mediated hyperactivation of phosphatidylinositol 3-kinase. Am J Pathol 177(6):3125-32. [PubMed: 21037083]  [MGI Ref ID J:167633]

Deane JA; Kharas MG; Oak JS; Stiles LN; Luo J; Moore TI; Ji H; Rommel C; Cantley LC; Lane TE; Fruman DA. 2007. T-cell function is partially maintained in the absence of class IA phosphoinositide 3-kinase signaling. Blood 109(7):2894-902. [PubMed: 17164340]  [MGI Ref ID J:143667]

Engelman JA; Chen L; Tan X; Crosby K; Guimaraes AR; Upadhyay R; Maira M; McNamara K; Perera SA; Song Y; Chirieac LR; Kaur R; Lightbown A; Simendinger J; Li T; Padera RF; Garcia-Echeverria C; Weissleder R; Mahmood U; Cantley LC; Wong KK. 2008. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 14(12):1351-6. [PubMed: 19029981]  [MGI Ref ID J:142254]

Hill JW; Williams KW; Ye C; Luo J; Balthasar N; Coppari R; Cowley MA; Cantley LC; Lowell BB; Elmquist JK. 2008. Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice. J Clin Invest 118(5):1796-805. [PubMed: 18382766]  [MGI Ref ID J:136147]

Hill JW; Xu Y; Preitner F; Fukuda M; Cho YR; Luo J; Balthasar N; Coppari R; Cantley LC; Kahn BB; Zhao JJ; Elmquist JK. 2009. Phosphatidyl inositol 3-kinase signaling in hypothalamic proopiomelanocortin neurons contributes to the regulation of glucose homeostasis. Endocrinology 150(11):4874-82. [PubMed: 19819947]  [MGI Ref ID J:158221]

Ivanovic I; Allen DT; Dighe R; Le YZ; Anderson RE; Rajala RV. 2011. Phosphoinositide 3-kinase signaling in retinal rod photoreceptors. Invest Ophthalmol Vis Sci 52(9):6355-62. [PubMed: 21730346]  [MGI Ref ID J:181401]

Kaneko K; Ueki K; Takahashi N; Hashimoto S; Okamoto M; Awazawa M; Okazaki Y; Ohsugi M; Inabe K; Umehara T; Yoshida M; Kakei M; Kitamura T; Luo J; Kulkarni RN; Kahn CR; Kasai H; Cantley LC; Kadowaki T. 2010. Class IA phosphatidylinositol 3-kinase in pancreatic beta cells controls insulin secretion by multiple mechanisms. Cell Metab 12(6):619-32. [PubMed: 21109194]  [MGI Ref ID J:168115]

Kharas MG; Janes MR; Scarfone VM; Lilly MB; Knight ZA; Shokat KM; Fruman DA. 2008. Ablation of PI3K blocks BCR-ABL leukemogenesis in mice, and a dual PI3K/mTOR inhibitor prevents expansion of human BCR-ABL+ leukemia cells. J Clin Invest 118(9):3038-50. [PubMed: 18704194]  [MGI Ref ID J:140852]

Luo J; Sobkiw CL; Hirshman MF; Logsdon MN; Li TQ; Goodyear LJ; Cantley LC. 2006. Loss of class IA PI3K signaling in muscle leads to impaired muscle growth, insulin response, and hyperlipidemia. Cell Metab 3(5):355-66. [PubMed: 16679293]  [MGI Ref ID J:129646]

Oak JS; Chen J; Peralta RQ; Deane JA; Fruman DA. 2009. The p85beta regulatory subunit of phosphoinositide 3-kinase has unique and redundant functions in B cells. Autoimmunity 42(5):447-58. [PubMed: 19811262]  [MGI Ref ID J:172476]

Oak JS; Deane JA; Kharas MG; Luo J; Lane TE; Cantley LC; Fruman DA. 2006. Sjogren's syndrome-like disease in mice with T cells lacking class 1A phosphoinositide-3-kinase. Proc Natl Acad Sci U S A 103(45):16882-7. [PubMed: 17071741]  [MGI Ref ID J:117150]

Park SW; Zhou Y; Lee J; Lu A; Sun C; Chung J; Ueki K; Ozcan U. 2010. The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation. Nat Med 16(4):429-37. [PubMed: 20348926]  [MGI Ref ID J:159304]

Rajala A; Dighe R; Agbaga MP; Anderson RE; Rajala RV. 2013. Insulin receptor signaling in cones. J Biol Chem 288(27):19503-15. [PubMed: 23673657]  [MGI Ref ID J:199655]

Taniguchi CM; Aleman JO; Ueki K; Luo J; Asano T; Kaneto H; Stephanopoulos G; Cantley LC; Kahn CR. 2007. The p85alpha regulatory subunit of phosphoinositide 3-kinase potentiates c-Jun N-terminal kinase-mediated insulin resistance. Mol Cell Biol 27(8):2830-40. [PubMed: 17283057]  [MGI Ref ID J:121377]

Taniguchi CM; Kondo T; Sajan M; Luo J; Bronson R; Asano T; Farese R; Cantley LC; Kahn CR. 2006. Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and PKClambda/zeta. Cell Metab 3(5):343-53. [PubMed: 16679292]  [MGI Ref ID J:129647]

Taniguchi CM; Tran TT; Kondo T; Luo J; Ueki K; Cantley LC; Kahn CR. 2006. Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN. Proc Natl Acad Sci U S A 103(32):12093-7. [PubMed: 16880400]  [MGI Ref ID J:111784]

Taniguchi CM; Winnay J; Kondo T; Bronson RT; Guimaraes AR; Aleman JO; Luo J; Stephanopoulos G; Weissleder R; Cantley LC; Kahn CR. 2010. The phosphoinositide 3-kinase regulatory subunit p85alpha can exert tumor suppressor properties through negative regulation of growth factor signaling. Cancer Res 70(13):5305-15. [PubMed: 20530665]  [MGI Ref ID J:161603]

Winnay JN; Boucher J; Mori MA; Ueki K; Kahn CR. 2010. A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein response. Nat Med 16(4):438-45. [PubMed: 20348923]  [MGI Ref ID J:159307]

Winnay JN; Dirice E; Liew CW; Kulkarni RN; Kahn CR. 2014. p85alpha deficiency protects beta-cells from endoplasmic reticulum stress-induced apoptosis. Proc Natl Acad Sci U S A 111(3):1192-7. [PubMed: 24395790]  [MGI Ref ID J:206472]

Yang FC; Chen S; Robling AG; Yu X; Nebesio TD; Yan J; Morgan T; Li X; Yuan J; Hock J; Ingram DA; Clapp DW. 2006. Hyperactivation of p21 and PI3K cooperate to alter murine and human neurofibromatosis type 1-haploinsufficient osteoclast functions. J Clin Invest 116(11):2880-91. [PubMed: 17053831]  [MGI Ref ID J:114609]

de Souza AJ; Oak JS; Jordanhazy R; DeKruyff RH; Fruman DA; Kane LP. 2008. T cell Ig and mucin domain-1-mediated T cell activation requires recruitment and activation of phosphoinositide 3-kinase. J Immunol 180(10):6518-26. [PubMed: 18453570]  [MGI Ref ID J:134962]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   101043 B6129SF1/J (approximate)
   101045 B6129SF2/J (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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