Overview

Mice homozygous for the GCN2.KO4^conditional allele (also called GCN2.KO4c) have loxP sites flanking exon XII of the eukaryotic translation initiation factor 2 alpha kinase 4 (Eif2ak4 or GCN2) targeted gene, and may be useful in generating conditional mutations for studying eIF2 (eukaryotic initiation factor 2) phosphorylation in response to environmental stresses (amino acid starvation, proteasome inhibition and UV irradiation).

Donating Investigator

David Ron, NYU School of Medicine

Genetic overview

Genetic Background	Generation
	?+pN1 (2019-11-19 00:00:00)

Eif2ak4^tm1.1Dron

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Eif2ak4	eukaryotic translation initiation factor 2 alpha kinase 4

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Research Applications

Cancer Research
Neurobiology Research
Research Tools
Immunology, Inflammation and Autoimmunity Research
Apoptosis Research
Cell Biology Research

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Base Price

Starting at:

$255.00 Domestic price for female

510.00 Domestic price for breeder pair

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the GCN2.KO4^conditional allele (also called GCN2.KO4c) are viable and fertile, with loxP sites flanking exon XII of the targeted gene. When bred to mice that express Cre recombinase, the resulting offspring will have this region (containing amino acid residues 606-648 encoding the critical lysine 618 required for kinase activity) deleted in the cre-expressing tissue(s). GCN2 is a protein kinase that phosphorylates eIF2 (eukaryotic initiation factor 2) in response to environmental stresses (amino acid starvation, proteasome inhibition and UV irradiation) resulting in a reduction of global translation and activation of stress-related transcription factors (such as NF-kappaB). These GCN2.KO4^conditional mice may be useful in studies related to eIF2 phosphorylation in response to environmental stresses.

Of note, mice with a traditional "knockout" (deletion of exon XII) are also available (see Stock No. 008240).

When bred to a strain expressing Cre recombinase in the central and peripheral nervous system (see Stock No. 003771 for example), this mutant mouse strain may be useful in studies of amino acid homeostasis.

Development

A targeting vector was designed to place a loxP site just upstream of, and a loxP-flanked Neo resistance cassette just downstream of exon XII of the targeted gene. The construct was electroporated into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were then transiently transfected with a Cre recombinase expression plasmid. The resulting ES cells with the selection cassette removed and a single loxP site remaining on each side of exon XII were injected into recipient blastocysts to generate chimeric mice. The donating investigator reports that the resulting GCN2.KO4^conditional (also called GCN2.KO4c) mutant mice were then maintained on a mixed C57BL/6;129 genetic background and bred as homozygotes prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6J for at least one generation to establish the colony.

Control Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Maurin AC; Jousse C; Averous J; Parry L; Bruhat A; Cherasse Y; Zeng H; Zhang Y; Harding HP; Ron D; Fafournoux P. 2005. The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores. Cell Metab 1(4):273-7PubMed: 16054071 MGI: J:129841

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Genetics

Eif2ak4^tm1.1Dron

Allele Symbol: Eif2ak4^tm1.1Dron

Allele Name	targeted mutation 1.1, David Ron
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Eif2ak4^tm1.1Dron; targeted mutation 1.1, David Ron
Gene Symbol and Name	Eif2ak4, eukaryotic translation initiation factor 2 alpha kinase 4
Gene Synonym(s)	PVOD2; GCN2
Strain of Origin	129S6/SvEvTac
Chromosome	2
Molecular Note	Exon 12 was flanked by loxP sites by inserting a loxP sequence into the EcorRI site in intron 11, and a floxed neomycin resistance cassette into the NheI site of intron 12. After homologous recombination, Cre was transiently expressed and ES cells were selected that had the neomycin cassette removed. Geneotypes were confirmed by PCR. The floxed exon 12 encodes a region of the kinase domain required for ATP binding. In addition, removal of this exon leads to a frameshift mutation with multiple stop codons.
Mutations Made By	David Ron, NYU School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Cancer Research
- Growth Factors/Receptors/Cytokines
Neurobiology Research
- Behavioral and Learning Defects
  - genes regulating preferences to alcohol and stress
- Cre-lox System
  - loxP-flanked Sequences
Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis
  - Mutagenesis and Transgenesis: Cre-lox System
  - Mutagenesis and Transgenesis: transcriptional activation
- Cre-lox System
  - loxP-flanked Sequences
- Apoptosis Research
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules
- Growth Factors/Receptors/Cytokines
- Inflammation
Apoptosis Research
- Endogenous Regulators
Cell Biology Research
- Protein Processing
- DNA Damage Response
- Signal Transduction
- Transcriptional Regulation

Mammalian Phenotype Terms by Genotype

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

Genotype: Eif2ak4^tm1.1Dron/Eif2ak4^tm1.1Dron Tg(Nes-cre)1Kln/0
involves: 129S6/SvEvTac * C57BL/6 * SJL

behavior/neurological phenotype

abnormal food preference
- mice consume more of a leucine-deficient chow after 1 hour compared to wild-type mice that consume almost 30% less
- mice consume under 10% less leucine-deficient chow after 4 hours compared to wild-type mice that consume around 25% less
- mice have much less of an aversion to diets lacking an essential amino acid
- similar responses are observed in threonine-deficient diet

References

Maurin AC; Jousse C; Averous J; Parry L; Bruhat A; Cherasse Y; Zeng H; Zhang Y; Harding HP; Ron D; Fafournoux P. 2005. The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores. Cell Metab 1(4):273-7PubMed: 16054071 MGI: J:129841

Additional - Eif2ak4^tm1.1Dron related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Eif2ak4^tm1.1Dron
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Heterozygote
Citation
When using the B6;129-Eif2ak4^tm1.1Dron/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008452 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Available for Pre-order

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Eif2ak4<tm1.1Dron>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

Related Products and Services

Frozen Mouse Embryo	B6;129-Eif2ak4<tm1.1Dron>/J	$2595.00
Frozen Mouse Embryo	B6;129-Eif2ak4<tm1.1Dron>/J	$2595.00
Frozen Mouse Embryo	B6;129-Eif2ak4<tm1.1Dron>/J	$3373.50
Frozen Mouse Embryo	B6;129-Eif2ak4<tm1.1Dron>/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.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Eif2ak4tm1.1Dron

Allele Symbol: Eif2ak4tm1.1Dron

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Eif2ak4tm1.1Dron/Eif2ak4tm1.1Dron Tg(Nes-cre)1Kln/0involves: 129S6/SvEvTac * C57BL/6 * SJL

behavior/neurological phenotype

References

Additional - Eif2ak4tm1.1Dron related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Related Products and Services

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

Eif2ak4^tm1.1Dron

Allele Symbol: Eif2ak4^tm1.1Dron

Genotype: Eif2ak4^tm1.1Dron/Eif2ak4^tm1.1Dron Tg(Nes-cre)1Kln/0
involves: 129S6/SvEvTac * C57BL/6 * SJL

Additional - Eif2ak4^tm1.1Dron related