Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   22-SEP-11 Species laboratory mouse Generation F?+N1F5 (12-NOV-12) Generation Definitions   Donating Investigator Lewis C Cantley,   Beth Israel Deaconess Medical Center

Description
Mice homozygous for this p85α^loxP 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 p85α^loxP 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 p85α^loxP 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 p85α^loxP mice (with single frt site remaining upstream of the floxed exon 7) were bred together to remove the Rosa26-FLP allele. p85α^loxP 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 p85α^loxP colony.

Prior to arrival at The Jackson Laboratory Repository, p85α^loxP 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 p85α^loxP 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 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.

Pik3r1^tm1Lca/Pik3r1^tm1Lca 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 (Floxed/Frt)
Common Name(s)		P85alphaloxP; Pik3r1flox; pik3r1loxP;
Mutation Made By		Lewis Cantley,   Beth Israel Deaconess Medical Center
Strain of Origin		129S6/SvEvTac
Gene Symbol and Name		Pik3r1, phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha)
Chromosome		13
Gene Common Name(s)		AA414921; AGM7; GRB1; 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

Pik3r1^tm1Lca, 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

Pik3r1^tm1Lca 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]

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]

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

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   22-SEP-11
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

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"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "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 the 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 or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

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 and PRODUCTS 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.