Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.129S6-Arts1tm1Luc/J    (Changed: 12-DEC-07 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Luc Van Kaer,   Vanderbilt University School of Medicine

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 Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

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   (MGI Ref ID J:122479)
• • decreased level of surface class I molecules
    • heterozygous animals show intermediate expression levels of class I molecules between homozygotes and wild-type mice   (MGI Ref ID J:122479)

Erap1^tm1Luc/Erap1^tm1Luc

        involves: 129S6/SvEvTac

• immune system phenotype
• *normal* immune system phenotype
  • CD8+ T cell development is normal in homozygous mice   (MGI Ref ID J:122479)
  • null mice show insignificant differences in response to infection with an influenza virus   (MGI Ref ID J:122479)
• • abnormal antigen presentation
    • 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   (MGI Ref ID J:122479)
    • 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   (MGI Ref ID J:122479)
    • 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   (MGI Ref ID J:122479)
    • mutant macrophages infected with OVA-expressing bacteria are defective in antigen presentation to OVA specific T cells   (MGI Ref ID J:122479)
    • dendritic cells infected with LCMV show enhanced reactivity with gp33 (immunodominant LCMV-derived epitope)-T cells compared to wild-type cells   (MGI Ref ID J:122479)
  • • decreased level of surface class I molecules
      • 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   (MGI Ref ID J:122479)
      • 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   (MGI Ref ID J:122479)
    • increased level of surface class I molecules   (MGI Ref ID J:122479)
  • 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   (MGI Ref ID J:122479)
  • • abnormal CD8-positive 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   (MGI Ref ID J:122479)

View Research Applications

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
      T cell deficiency
      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
      T cell deficiency
      T cell deficiency, xenograft/transplant host
Toxicology Research
      xenograft/transplant host

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Erap1tm1Luc
Allele Name		targeted mutation 1, Luc Van Kaer
Allele Type		Targeted (knock-out)
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; 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.RT-PCR verified absence of mRNA in splenocytes and no protein is detected in hepatocytes by immunoblot. [MGI Ref ID J:122479]

Genotyping

Genotyping Information

Genotyping Protocols

Erap1^tm1Luc, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

Additional References

Erap1^tm1Luc related

Dragovic SM; Hill T; Christianson GJ; Kim S; Elliott T; Scott D; Roopenian DC; Van Kaer L; Joyce S. 2011. Proteasomes, TAP, and endoplasmic reticulum-associated aminopeptidase associated with antigen processing control CD4+ Th cell responses by regulating indirect presentation of MHC class II-restricted cytoplasmic antigens. J Immunol 186(12):6683-92. [PubMed: 21572029]  [MGI Ref ID J:175483]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice can be bred together.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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