Overview

These p85α^loxP 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.

Donating Investigator

Lewis C Cantley, Beth Israel Deaconess Medical Center

Genetic overview

Genetic Background	Generation

Pik3r1^tm1Lca

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Pik3r1	phosphoinositide-3-kinase regulatory subunit 1

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Cancer Research
Research Tools
Cell Biology Research
Diabetes and Obesity Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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 Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

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):9491-502PubMed: 16227599 MGI: 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):9739-44PubMed: 18621722 MGI: J:137878

View All References

Genetics

Pik3r1^tm1Lca

Allele Symbol: Pik3r1^tm1Lca

Allele Name	targeted mutation 1, Lewis C Cantley
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	P85alphaloxP; Pik3r1^flox; pik3r1^loxP
Gene Symbol and Name	Pik3r1, phosphoinositide-3-kinase regulatory subunit 1
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	13
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.
Mutations Made By	Lewis Cantley, Beth Israel Deaconess Medical Center

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
- Intracellular Signaling Molecules
Cancer Research
- Other
- Genes Regulating Growth and Proliferation
- Growth Factors/Receptors/Cytokines
Research Tools
- Cancer Research
- Cell Biology Research
- Cre-lox System
  - loxP-flanked Sequences
- Reproductive Biology Research
  - Cre-lox System
- Developmental Biology Research
  - Cre-lox System
- Genetics Research
  - Mutagenesis and Transgenesis: Cre-lox System
Cell Biology Research
- Genes Regulating Growth and Proliferation
- Cell Cycle Regulation
- Transcriptional Regulation
- Signal Transduction
Diabetes and Obesity Research
- Insulin Receptors and Growth Factors

Mammalian Phenotype Terms by Genotype

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

Genotype: Pik3r1^tm1Lca/Pik3r1^tm1Lca Tg(Ckmm-cre)5Khn/0
involves: 129S6/SvEvTac * C57BL/6 * FVB

normal phenotype

no abnormal phenotype detected
- Normal - mutants are viable and fertile, with no gross abnormalities and normal muscle morphology

Genotype: Pik3r1^tm1Lca/Pik3r1^tm1Lca Tg(OPN1LW-cre)4Yzl/0
involves: 129S6/SvEvTac * FVB/N

nervous system phenotype

abnormal retinal cone cell morphology
- progressive disorganization of synaptic ultrastructure is seen in the terminals of surviving cones at 6 and 12 months of age but not at 1 month

abnormal ribbon synapse morphology
- cone terminals in the retina ribbon synaptic complexes are reduced, flat contacts are sometimes located adjacent to synaptic ribbons, and interactions with postsynaptic processes appear disorganized

abnormal synapse morphology
- progressive disorganization of synaptic ultrastructure is seen in the terminals of surviving cones at 6 and 12 months of age but not at 1 month

retinal cone cell degeneration
- Normal - however, the overall morphology and structural integrity of the retina are similar to wild-type mice at 1, 6, and 12 months of age
- retinas show patchy regions devoid of cones by 6 months and cone photoreceptor loss is further exacerbated by 12 months of age
- the inferior meridian region of the retinas shows greater cone loss than the superior region at 6 months but by 12 months, similar loss of cones is seen in both regions

vision/eye phenotype

abnormal retinal cone cell morphology
- progressive disorganization of synaptic ultrastructure is seen in the terminals of surviving cones at 6 and 12 months of age but not at 1 month

decreased b wave amplitude
- Normal - however, scotopic ERG recordings of rod photoreceptors (scotopic a-wave) are normal at 1, 6, and 12 months of age
- photopic ERG b-wave amplitudes are decreased at 6 months, but not 1 month of age, and decrease progressively to 12 months
- scotopic b-wave amplitudes are lower at 6 and 12 months of age compared with control floxed mice but are not different from control cre-only expressing mice

retinal cone cell degeneration
- Normal - however, the overall morphology and structural integrity of the retina are similar to wild-type mice at 1, 6, and 12 months of age
- retinas show patchy regions devoid of cones by 6 months and cone photoreceptor loss is further exacerbated by 12 months of age
- the inferior meridian region of the retinas shows greater cone loss than the superior region at 6 months but by 12 months, similar loss of cones is seen in both regions

References

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):9491-502PubMed: 16227599 MGI: 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):9739-44PubMed: 18621722 MGI: J:137878

Additional - Pik3r1^tm1Lca related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Pik3r1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Pik3r1^tm1Lca/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012871 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 for Pik3r1<tm1Lca>

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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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General Terms and Conditions

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

Pik3r1tm1Lca

Allele Symbol: Pik3r1tm1Lca

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Pik3r1tm1Lca/Pik3r1tm1Lca Tg(Ckmm-cre)5Khn/0involves: 129S6/SvEvTac * C57BL/6 * FVB

normal phenotype

Genotype: Pik3r1tm1Lca/Pik3r1tm1Lca Tg(OPN1LW-cre)4Yzl/0involves: 129S6/SvEvTac * FVB/N

nervous system phenotype

vision/eye phenotype

References

Additional - Pik3r1tm1Lca 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

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

Pik3r1^tm1Lca

Allele Symbol: Pik3r1^tm1Lca

Genotype: Pik3r1^tm1Lca/Pik3r1^tm1Lca Tg(Ckmm-cre)5Khn/0
involves: 129S6/SvEvTac * C57BL/6 * FVB

Genotype: Pik3r1^tm1Lca/Pik3r1^tm1Lca Tg(OPN1LW-cre)4Yzl/0
involves: 129S6/SvEvTac * FVB/N

Additional - Pik3r1^tm1Lca related