Overview

These mutant mice may be useful in immunological studies exploring the in vivo role of ERAP1 in optimizing peptides for presentation by MHC class I molecules.

Donating Investigator

Dr. Luc Van Kaer, Vanderbilt University School of Medicine

Genetic overview

Genetic Background	Generation

Erap1^tm1Luc

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Erap1	endoplasmic reticulum aminopeptidase 1

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Research Applications

Research Tools
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Homozygous mutant mice are viable and fertile. The absence of mRNA in splenocyte and of protein in hepatocyte lysates is confirmed via RT-PCR and immunoblot, respectively. Homozygous mutants display reduced cell surface expression of MHC class Ia and Ib molecules, altered presentation of self- and foreign-antigens, and defective CD8⁺ T-cell responses against class I-presented antigens. These mutant mice may be useful in immunological studies exploring ERAP1's role in vivo in optimizing peptides for presentation by MHC class I molecules.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector was designed to replace a fragment from intron 4 up to the 5' end of exon 6 (which contains the sequence encoding the Zinc-binding motif in the putative active site of the endogenous protein) with a neomycin resistance cassette. The construct was electroporated into 129S6/SvEvTac-derived TL-1 embryonic stem (ES) cells. Correctly targeted ES cells were microinjected into blastocysts and the resulting chimeric mice were bred to C57BL/6 to generate heterozygotes. These mice were then backcrossed to C57BL/6 for at least 10 generations prior to arrival at The Jackson Laboratory.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Yan J; Parekh VV; Mendez-Fernandez Y; Olivares-Villagomez D; Dragovic S; Hill T; Roopenian DC; Joyce S; Van Kaer L. 2006. In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules. J Exp Med 203(3):647-59PubMed: 16505142 MGI: J:122479

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Genetics

Erap1^tm1Luc

Allele Symbol: Erap1^tm1Luc

Allele Name	targeted mutation 1, Luc Van Kaer
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	ERAP1^-
Gene Symbol and Name	Erap1, endoplasmic reticulum aminopeptidase 1
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	13
Molecular Note	A targeting vector was designed to replace a 600 kb fragment from intron 4 up to the 5' end of exon 6 (which contains the sequence encoding the Zinc-binding motif in the putative active site of the endogenous protein) with a neomycin resistance cassette. RT-PCR verified absence of mRNA in splenocytes and no protein is detected in hepatocytes by immunoblot.
Mutations Made By	Dr. Luc Van Kaer, Vanderbilt University School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - T cell deficiency, xenograft/transplant host
  - MHC class I deficiency
  - T cell deficiency
- Cancer Research
  - xenograft/transplant host
- Toxicology Research
  - xenograft/transplant host
Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
- Immunodeficiency
  - MHC class I deficiency
  - specific T cell deficiency
  - T cell deficiency
Internal/Organ Research
- Lymphoid Tissue Defects
  - T cell deficiency

Mammalian Phenotype Terms by Genotype

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

Genotype: Erap1^tm1Luc/Erap1^tm1Luc
involves: 129S6/SvEvTac

hematopoietic system phenotype

abnormal CD8-positive, alpha-beta T cell physiology
- 7 days after immunization of mutant mice with OVA-loaded Tap1-null cells, stimulation of splenocytes with OVA peptide revealed a 3- to 4-fold reduction in generation of OVA-specific CD8+ T cells responses in vivo

abnormal lymphocyte physiology
- decay of surface K^b and d^b molecules on brefeldin A-treated cells is increased compared to wild-type, but is less pronounced than on Tapbp-null treated cells

mammalian phenotype

immune system phenotype
- CD8+ T cell development is normal in homozygous mice
- null mice show insignificant differences in response to infection with an influenza virus

immune system phenotype

abnormal antigen presentation
- a panel of Qa-1^b-restricted, alloreactive CTL clones each show a significant reduction in capacity to lyse mutant splenic cells compared with wild-type cells
- defective presentation of self-antigens to class I-restricted cytotoxic T lymphocytes (CTLs) is observed in null-cells; defects in reactivity of two H60-specific CTL clones and an HY-specific clone with null cells is seen, while H4^b-specific clones react similarly with null splenocytes and wild-type cells, and an H13^b-specific clone reacted with null cells more strongly than with wild-type
- dendritic cells infected with LCMV show enhanced reactivity with gp33 (immunodominant LCMV-derived epitope)-T cells compared to wild-type cells
- ic H-2K^b-restricted T cell hybridoma
- mutant macrophages infected with OVA-expressing bacteria are defective in antigen presentation to OVA specific T cells
- ones react similarly with null splenocytes and wild-type cells, and an H13^b-specific clone reacted with null cells more strongly than with wild-type
- when ovalbumin is introduced to cell cytoplasm by osmotic shock, mutant cells show impairment in presentation of OVA-derived epitopes; bone marrow-derived dendritic cells and LPS-induced lymphoblasts are also defective in presenting OVA to a an OVA-specific H-2K^b-restricted T cell hybridoma

abnormal CD8-positive, alpha-beta T cell physiology
- 7 days after immunization of mutant mice with OVA-loaded Tap1-null cells, stimulation of splenocytes with OVA peptide revealed a 3- to 4-fold reduction in generation of OVA-specific CD8+ T cells responses in vivo

abnormal lymphocyte physiology
- decay of surface K^b and d^b molecules on brefeldin A-treated cells is increased compared to wild-type, but is less pronounced than on Tapbp-null treated cells

decreased level of surface class I molecules
- levels of H-2K^b and H-2D^b are reduced ~40 and 50% respectively; extent of surface display of nonclassical class I molecule Qa-2 is reduced ~35% compared to wild-type cells
- reduction in surface expression of H-2K^b and H-2D^b molecules on total mononuclear cells in spleen, lymph node, and blood including splenic dendritic cells, T cells, and B cells, as well as fibroblast cell lines from mice

increased level of surface class I molecules

Genotype: Erap1^tm1Luc/Erap1⁺
involves: 129S6/SvEvTac

immune system phenotype

abnormal antigen presentation
- heterozygous cells show impairment in processing OVA for surface display by K^b

decreased level of surface class I molecules
- heterozygous animals show intermediate expression levels of class I molecules between homozygotes and wild-type mice

References

Yan J; Parekh VV; Mendez-Fernandez Y; Olivares-Villagomez D; Dragovic S; Hill T; Roopenian DC; Joyce S; Van Kaer L. 2006. In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules. J Exp Med 203(3):647-59PubMed: 16505142 MGI: J:122479

Additional - Erap1^tm1Luc related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Erap1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice can be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129S6-Erap1^tm1Luc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #006413 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 Erap1<tm1Luc>

Related Products and Services

Frozen Mouse Embryo	B6.129S6-Erap1<tm1Luc>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S6-Erap1<tm1Luc>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S6-Erap1<tm1Luc>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129S6-Erap1<tm1Luc>/J Frozen Embryo	$3373.50

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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. 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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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Erap1tm1Luc

Allele Symbol: Erap1tm1Luc

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Erap1tm1Luc/Erap1tm1Lucinvolves: 129S6/SvEvTac

hematopoietic system phenotype

mammalian phenotype

immune system phenotype

Genotype: Erap1tm1Luc/Erap1+involves: 129S6/SvEvTac

immune system phenotype

References

Additional - Erap1tm1Luc 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

Erap1^tm1Luc

Allele Symbol: Erap1^tm1Luc

Genotype: Erap1^tm1Luc/Erap1^tm1Luc
involves: 129S6/SvEvTac

Genotype: Erap1^tm1Luc/Erap1⁺
involves: 129S6/SvEvTac

Additional - Erap1^tm1Luc related