Overview

Also Known As: eIF2alpha^S51A

These Eif2s1 knock-out mice lack translational and transcriptional regulation in the endoplasmic reticulum. These mice maybe useful in diabetes research.

Donating Investigator

Randal J Kaufman, Sanford Burnham Prebys Medical Discovery Institute

Genetic overview

Genetic Background	Generation

Eif2s1^tm1Rjk

Allele Type	Gene Symbol	Gene Name
Targeted (Not Specified)	Eif2s1	eukaryotic translation initiation factor 2, subunit 1 alpha

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Research Applications

Endocrine Deficiency Research
Apoptosis Research
Cell Biology Research
Diabetes and Obesity Research
Metabolism Research
Developmental Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The Eif2a^S51A mutation in these mice prevents phosphorylation of the α subunit of eIF2. Phosphorylation of eIF2α in the endoplasmic reticulum (ER) is required for translational regulation, transcriptional induction, and survival in response to ER stress. EIF2α translational regulation is also required for the maintenance of blood glucose and pancreatic insulin content. Homozygotes die within 18 hr after birth due to hypoglycemia associated with defective gluconeogenesis. Homozygous mutant embryos and neonates displayed a deficiency in pancreatic β cells and an increase in circulating insulin. Heterozygotes are viable and fertile. On a high fat diet, heterozygous mice develop diabetes due to unregulated proinsulin translation. These mice also exhibit defective ER cargo trafficking, increased oxidative damage, reduced expression of stress response and beta-cell-specific genes, and apoptosis.

Development

Three base pair substitutions were introduced into exon 2 of the mouse eIF2α (Eif2s1) resulting in a single amino acid substitution of serine to alanine at codon 51 (S51A) within the phosphorylation site of the protein. A loxP-flanked neo cassette in reverse-orientation to the gene was inserted 200 bp upstream of exon 2. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient C57BL/6 blastocysts and chimeric males were bred with C57BL/6 females to establish the colony. Mutant mice were bred with ZP3-Cre transgenic mice (on a C57BL/6 genetic background) to remove the neo selection cassette. The donating investigator reported that these eIF2α^S51A mice were bred to C57BL/6J mice for at least ten generations (see SNP note below), and the ZP3-Cre transgene was removed. Upon arrival at The Jackson Laboratory Repository, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. 2 the 27 markers throughout the genome were segregating between B6J and 129, suggesting an incomplete backcross. Also, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Scheuner D; Song B; McEwen E; Liu C; Laybutt R; Gillespie P; Saunders T; Bonner-Weir S; Kaufman RJ. 2001. Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol Cell 7(6):1165-76PubMed: 11430820 MGI: J:70004

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Genetics

Eif2s1^tm1Rjk

Allele Symbol: Eif2s1^tm1Rjk

Allele Name	targeted mutation 1, Randal J Kaufman
Allele Type	Targeted (Not Specified)
Allele Synonym(s)	Eif2s1^tm1Rjk; targeted mutation 1, Randal J Kaufman
Gene Symbol and Name	Eif2s1, eukaryotic translation initiation factor 2, subunit 1 alpha
Gene Synonym(s)	eukaryotic translation initiation factor 2A; 0910001O23Rik; 2410026C18Rik; 0910001O23Rik; Eif2a; EIF-2; EIF-2A; EIF-2alpha; EIF2; EIF2A; eIF2alpha; RIKEN cDNA 0910001O23 gene; RIKEN cDNA 2410026C18 gene; 2410026C18Rik; Eif2a
Promoter	Eif2s1, eukaryotic translation initiation factor 2, subunit 1 alpha, mouse, laboratory
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	12
Molecular Note	A serine to alanine substitution at a phosphorylation site at position 51 (S51A) of exon 2 was introduced, and a floxed neomycin resistance cassette was inserted into the upstream intron for positive selection. The floxed neo cassette was removed by cre-mediated recombination leaving behind a single loxP site and the S51A mutation. Western blot analysis of mouse embryonic fibroblasts derived from homozygous mutant animals confirmed expression of the mutant allele.
Mutations Made By	Randal Kaufman, Sanford Burnham Prebys Medical Discovery Institute

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Endocrine Deficiency Research
- Pancreas Defects
Apoptosis Research
Cell Biology Research
- Transcriptional Regulation
- Protein Processing
Diabetes and Obesity Research
- Hypoglycemia
- Hyperinsulinemia
Metabolism Research
- Free Radical Research
Developmental Biology Research
- Postnatal Lethality
  - Homozygous

Mammalian Phenotype Terms by Genotype

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

Genotype: Eif2s1^tm1Rjk/Eif2s1^tm1Rjk
involves: 129S1/Sv * 129X1/SvJ

behavior/neurological phenotype

abnormal suckling behavior
- neonates did not nurse

endocrine/exocrine gland phenotype

decreased insulin secretion
- insulin level of neonatal pancreas was 35% of wild-type

homeostasis/metabolism phenotype

decreased circulating insulin level
- neonatal serum insulin level was 20% of wild-type

decreased insulin secretion
- insulin level of neonatal pancreas was 35% of wild-type

hypoglycemia
- severe hypoglycemia ensued 6-9 hours after birth

mortality/aging

neonatal lethality, complete penetrance
- neonates died within 18 hours after birth

References

Scheuner D; Song B; McEwen E; Liu C; Laybutt R; Gillespie P; Saunders T; Bonner-Weir S; Kaufman RJ. 2001. Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol Cell 7(6):1165-76PubMed: 11430820 MGI: J:70004

Additional - Eif2s1^tm1Rjk related

Technical Support

Contact Technical Support

Genotyping Protocols
- Probe: Generic Cre Probe
- Standard PCR: Eif2s1^tm1Rjk
- Melt Curve Analysis: Eif2s1^tm1Rjk
- MELT: Generic Cre Melt Curve Analysis
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). The donating investigator reports that homozygotes die within 18 hours after birth due to hypoglycemia. Heterozygous offspring survival is enhanced if cages containing newborns are not disturbed in the first 3 days after birth.
- Additional Breeding and Husbandry Support
Citation
When using the eIF2alpha^S51A mouse strain in a publication, please cite the originating article(s) and include JAX stock #017601 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	Genotype	Price
	Heterozygous or wildtype for Eif2s1<tm1Rjk>

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.

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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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Also Known As: eIF2alphaS51A

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Eif2s1tm1Rjk

Allele Symbol: Eif2s1tm1Rjk

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Eif2s1tm1Rjk/Eif2s1tm1Rjkinvolves: 129S1/Sv * 129X1/SvJ

behavior/neurological phenotype

endocrine/exocrine gland phenotype

homeostasis/metabolism phenotype

mortality/aging

References

Additional - Eif2s1tm1Rjk 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

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

Also Known As: eIF2alpha^S51A

Eif2s1^tm1Rjk

Allele Symbol: Eif2s1^tm1Rjk

Genotype: Eif2s1^tm1Rjk/Eif2s1^tm1Rjk
involves: 129S1/Sv * 129X1/SvJ

Additional - Eif2s1^tm1Rjk related