These Tapbp knock-out mice exhibit failure to assemble MHC class I peptide loading complexes.
Luc van Kaer, Vanderbilt University School of Medicine
Mice that are homozygous null for the Tapbp gene are viable and fertile. No Tapbp gene product is detected. Tapbp is an integral component of the MHC class I peptide loading complex. Expectedly, mice that are homozygous null for tapasin fail to assemble loading complexes. Overall expression of surface MHC class I expression is reduced. Although some class I molecules are able to translocate to the cell surface, they are unable to do so in association with peptide antigen. Antigen presenting cells from null animals had a slightly reduced ability to stimulate CD8+ T cells. A more significant defect is observed in the ability to present foreign antigen. CTL responses are differentially affected. Significant defects in positive and negative intrathymic selection are also observed.
A targeting construct containing a neomycin resistance gene was used to disrupt the fourth exon of the Tapbp gene. The construct was transfected into 129S6/SvEvTac-derived TL-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J mice.
|Allele Name||targeted mutation 1, Luc van Kaer|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Tapbp, TAP binding protein|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Insertion of a neomycin resistance cassette into the fourth exon.|
|Mutations Made By|| |
Andres Grandea III, Celltech
This strain originated on a B6;129S background and has been backcrossed to C57BL/6J for at least 6 generations before being made homozygous. This strain should be housed under pathogen free conditions similar to the Tap-deficient strain (002944).
When using the Tpn KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #003863 in your Materials and Methods section.