Overview

In this knockout strain the first 202 nucleotides of exon 2 of the inositol hexaphosphate kinase 2 (Ip6k2) gene is disrupted. These mice may be useful for studying the mechanisms of IP6K2-dependent tumorigenesis.

Donating Investigator

Daniel Lindner, Cleveland Clinic Main Campus

Genetic overview

Genetic Background	Generation

Ip6k2^tm1Dlin

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ip6k2	inositol hexaphosphate kinase 2

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Research Applications

Cancer Research
Cell Biology Research
Apoptosis Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

In this strain, a floxed-neo cassette replaces the first 202 nucleotides of exon 2 of the inositol hexaphosphate kinase 2 (Ip6k2) gene, abolishing gene expression. Homozygotes are viable, fertile, and normal in size. IP6K2 suppresses growth and increases apoptosis during cell stress by catalyzing the synthesis of inositol polyphosphates. These compounds are involved in the regulation of telomere length, protein phosphorylation, and cell growth and movement. After chronic exposure to the carcinogen 4-nitroquinoline 1-oxide (4-NQO) these mice exhibit a four-fold increase in the incidence of invasive squamous cell carcinoma (SCC) formation in the tongue, oral cavity, and esophagus. They also display relative resistance to ionizing radiation and exhibit increased survival following total body irradiation. Cells from these mice are relatively resistant to growth-suppression by interferon-β (IFN-β). These mice may be useful for studying the mechanisms of IP6K2-dependent tumorigenesis.

Development

A targeting vector was designed to replace the first 202 nucleotides of exon 2 of the inositol hexaphosphate kinase 2 (Ip6k2) gene with a loxP-flanked neomycin resistance (neo) cassette. The construct was electroporated into 129SvJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6J females to generate a colony of IHPK2- mice. These mice were maintained on a mixed B6;129S background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Suggestions

Heterozygote from the colony
Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Morrison BH; Haney R; Lamarre E; Drazba J; Prestwich GD; Lindner DJ. 2009. Gene deletion of inositol hexakisphosphate kinase 2 predisposes to aerodigestive tract carcinoma. Oncogene 28(25):2383-92PubMed: 19430495 MGI: J:151345

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Genetics

Ip6k2^tm1Dlin

Allele Symbol: Ip6k2^tm1Dlin

Allele Name	targeted mutation 1, D J Lindner
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	IHPK2^-
Gene Symbol and Name	Ip6k2, inositol hexaphosphate kinase 2
Gene Synonym(s)
Strain of Origin	129X1/SvJ
Chromosome	9
Molecular Note	The first 202 bp of exon 2 were replaced with a neo cassette. The absence of protein expression was confirmed by western blot analysis on tail snip extracts.
Mutations Made By	Daniel Lindner, Cleveland Clinic Main Campus

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Cancer Research
- Genes Regulating Growth and Proliferation
- Increased Tumor Incidence
  - Cell/Tissue Type
  - Other Tissues/Organs
Cell Biology Research
- Cell Motility Defects
- Defects in Extracellular Matrix Molecules
- Post-translational Processing
- Signal Transduction
- Vesicular Trafficking
Apoptosis Research

Mammalian Phenotype Terms by Genotype

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

Genotype: Ip6k2^tm1Dlin/Ip6k2^tm1Dlin
involves: 129X1/SvJ * Black Swiss * C57BL/6

cellular phenotype

abnormal cell death
- fibroblasts exhibit enhanced survival compared with wild-type cells

abnormal double-strand DNA break repair
- radiation treated fibroblasts exhibit increased double-strand break repair compared with similarly treated wild-type mice

increased fibroblast proliferation
- fibroblasts are resistant to the growth-suppressive effect of IFN-beta unlike wild-type cells
- fibroblasts exhibit increased colony-forming units compared with wild-type cells

mortality/aging

decreased mortality induced by ionizing radiation
- median survival after treatment with 8 Gy TBI is 17 days compared with 10.5 in similarly treated wild-type mice
- unlike in wild-type mice, long-term survival following treatment with 8 Gy is 12.5%

increased sensitivity to xenobiotic induced morbidity/mortality
- after 30 weeks of 4-nitroquinoline 1-oxide (4-NQO) exposure, no mice survive compared to 75% of similarly treated wild-type mice

neoplasm

increased incidence of tumors by chemical induction
- 100% of 4-NQO-treated mice develop carcinoma in the esophagus, oral cavity, or stomach compared with 25% of similarly treated wild-type mice that develop neoplastic lesions in these areas
- 4-NQO-treated mice exhibit vascular invasion unlike in similarly treated wild-type mice
- epithelial cell invasion into the muscularis is 4-fold more common in 4-NQO-treated mice than in similarly treated wild-type mice

digestive/alimentary phenotype

esophagus hyperplasia
- 4-NQO-treated mice develop mucosal hyperplasia and hyperkeratosis and, when advanced, distortion and partial obstruction of the lumen unlike in wild-type mice

growth/size/body region phenotype

esophagus hyperplasia
- 4-NQO-treated mice develop mucosal hyperplasia and hyperkeratosis and, when advanced, distortion and partial obstruction of the lumen unlike in wild-type mice

homeostasis/metabolism phenotype

abnormal double-strand DNA break repair
- radiation treated fibroblasts exhibit increased double-strand break repair compared with similarly treated wild-type mice

decreased mortality induced by ionizing radiation
- median survival after treatment with 8 Gy TBI is 17 days compared with 10.5 in similarly treated wild-type mice
- unlike in wild-type mice, long-term survival following treatment with 8 Gy is 12.5%

increased incidence of tumors by chemical induction
- 100% of 4-NQO-treated mice develop carcinoma in the esophagus, oral cavity, or stomach compared with 25% of similarly treated wild-type mice that develop neoplastic lesions in these areas
- 4-NQO-treated mice exhibit vascular invasion unlike in similarly treated wild-type mice
- epithelial cell invasion into the muscularis is 4-fold more common in 4-NQO-treated mice than in similarly treated wild-type mice

increased sensitivity to xenobiotic induced morbidity/mortality
- after 30 weeks of 4-nitroquinoline 1-oxide (4-NQO) exposure, no mice survive compared to 75% of similarly treated wild-type mice

References

Morrison BH; Haney R; Lamarre E; Drazba J; Prestwich GD; Lindner DJ. 2009. Gene deletion of inositol hexakisphosphate kinase 2 predisposes to aerodigestive tract carcinoma. Oncogene 28(25):2383-92PubMed: 19430495 MGI: J:151345

Additional - Ip6k2^tm1Dlin related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Ip6k2
- 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 B6;129-Ip6k2^tm1Dlin/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #016221 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 Ip6k2<tm1Dlin>

Related Products and Services

Frozen Mouse Embryo	B6;129-Ip6k2<tm1Dlin>/J	$2595.00
Frozen Mouse Embryo	B6;129-Ip6k2<tm1Dlin>/J	$2595.00
Frozen Mouse Embryo	B6;129-Ip6k2<tm1Dlin>/J	$3373.50
Frozen Mouse Embryo	B6;129-Ip6k2<tm1Dlin>/J	$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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ip6k2tm1Dlin

Allele Symbol: Ip6k2tm1Dlin

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ip6k2tm1Dlin/Ip6k2tm1Dlininvolves: 129X1/SvJ * Black Swiss * C57BL/6

cellular phenotype

mortality/aging

neoplasm

digestive/alimentary phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

References

Additional - Ip6k2tm1Dlin 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

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Ip6k2^tm1Dlin

Allele Symbol: Ip6k2^tm1Dlin

Genotype: Ip6k2^tm1Dlin/Ip6k2^tm1Dlin
involves: 129X1/SvJ * Black Swiss * C57BL/6

Additional - Ip6k2^tm1Dlin related