B6.129S6-Erap1^tm1Luc/J

Stock number: 006413
Research areas: Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

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.

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.

Allele

Symbol: Erap1^tm1Luc
Name: targeted mutation 1, Luc Van Kaer
MGI accession ID: MGI:3714520
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Erap1
Marker name: endoplasmic reticulum aminopeptidase 1
Chromosome: 13
Strain of origin: 129S6/SvEvTac
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.