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Former Name	B6.129S6-Arts1tm1Luc/J    (Changed: 12-DEC-07 )
Genes & Alleles	Erap1;   Erap1tm1Luc;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Targeted Mutation Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Donating Investigator Luc Van Kaer,   Vanderbilt University School of Medicine Generation N10+F1 (24-APR-08)

Strain 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.

Strain 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.

Mammalian Phenotype Terms assigned by genotype The following phenotype information may relate to a genetic background differing from this JAX® Mice strain. Erap1tm1Luc/Erap1+         involves: 129S6/SvEvTac immune system phenotype abnormal antigen presentation (MGI Ref ID J:122479) heterozygous cells show impairment in processing OVA for surface display by Kb decreased level of surface class I molecules (MGI Ref ID J:122479) heterozygous animals show intermediate expression levels of class I molecules between homozygotes and wild-type mice Erap1tm1Luc/Erap1tm1Luc         involves: 129S6/SvEvTac immune system phenotype *normal* immune system phenotype (MGI Ref ID J:122479) CD8+ T cell development is normal in homozygous mice null mice show insignificant differences in response to infection with an influenza virus abnormal antigen presentation (MGI Ref ID J:122479) 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 H4b-specific clones react similarly with null splenocytes and wild type cells, and an H13b-specific clone reacted with null cells more strongly than with wild-type a panel of Qa-1b-restricted, alloreactive CTL clones each show a significant reduction in capacity to lyse mutant splenic cells compared with wild-type cells 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-2Kb-restricted T cell hybridoma mutant macrophages infected with OVA-expressing bacteria are defective in antigen presentation to OVA specific T cells dendritic cells infected with LCMV show enhanced reactivity with gp33 (immunodominant LCMV-derived epitope)-T cells compared to wild-type cells decreased level of surface class I molecules (MGI Ref ID J:122479) reduction in surface expression of H-2Kb and H-2Db 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 levels of H-2Kb and H-2Db 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 increased level of surface class I molecules (MGI Ref ID J:122479) abnormal lymphocyte physiology (MGI Ref ID J:122479) decay of surface Kb and db molecules on brefeldin A-treated cells is increased compared to wild-type, but is less pronounced than on Tapbp-null treated cells abnormal CD8-positive T cell physiology (MGI Ref ID J:122479) 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

Gene & Allele Details

Allele Symbol		Erap1tm1Luc
Allele Name		targeted mutation 1, Luc Van Kaer
Common Name(s)		ERAP1-;
Mutation Made By		Luc Van Kaer,   Vanderbilt University School of Medicine
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TL1/TL-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Erap1, endoplasmic reticulum aminopeptidase 1
Chromosome		13
Gene Common Name(s)		A-LAP; ALAP; APPILS; ARTS-1; ARTS1; Arts1; ERAAP; ERAAP1; KIAA0525; MGC112613; PILS-AP; PILSAP; type 1 tumor necrosis factor receptor shedding aminopeptidase regulator;
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.The construct was electroporated into 129S6/SvEvTac-derived TL-1 embryonic stem (ES) cells. RT-PCR verified absence of mRNA in splenocytes and no protein is detected in hepatocytes by immunoblot. [MGI Ref ID J:122479]

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Genotyping Protocols

Erap1^tm1Luc

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice can be bred together.
Diet Information	LabDiet® 5K52/5K67

Additional Web Information

Congenic Nomenclature

Animal Health Reports

Room Number           AX12

Research Applications

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

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Immunodeficiency (MHC class I deficiency)
Immunodeficiency (T cell deficiency)
Immunodeficiency (specific T cell deficiency)

Internal/Organ Research
Lymphoid Tissue Defects (T cell deficiency)

Research Tools
Cancer Research (xenograft/transplant host)
Immunology and Inflammation Research (MHC class I deficiency)
Immunology and Inflammation Research (T cell deficiency)
Immunology and Inflammation Research (T cell deficiency) (xenograft/transplant host)
Toxicology Research (xenograft/transplant host)

References

Selected Reference(s)

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):647-59. [PubMed: 16505142]  [MGI Ref ID J:122479]

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Price and Supply Information

Strain Name:	B6.129S6-Erap1tm1Luc/J
Stock Number:	006413

Price Details

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Supply Details

Standard Supply	Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes	Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.
Licensing	See General Terms and Conditions below for Licensing and Use Restrictions
Control Information	View Control Information in Strain Details.

General Terms and Conditions

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For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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.

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