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Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N7 Donating Investigator Luc van Kaer, Vanderbilt University School of Medicine Description
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.Development
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.
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Congenic Nomenclature
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tapbptm1Luc/Tapbptm1Luc
involves: 129S6/SvEvTac * C57BL/6
- immune system phenotype
- 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 and Arts1-null cells
Tapbptm1Luc/Tapbptm1Luc
involves: 129S6/SvEvTac
- immune system phenotype
- abnormal antigen presentation via MHC class I (MGI Ref ID J:64177)
- cells infected with an influenza virus or a vaccinia virus minigene encoding an ovalbumin peptide were poorly recognized by nucleoprotein-specific Db-restricted T cell hybridoma or by cytotoxic T lymphocytes, respectively
- decreased level of surface class I molecules (MGI Ref ID J:64177)
- expression is 10-15% of that observed on wild-type cells, or 2 times the level on Tap1-deficient cells
- defective assembly of class I molecules (MGI Ref ID J:64177)
- mice display defective assembly of class I peptide-loading complexes
- in null cells, most heavy chains are thermolabile indicating lack of high-affinity peptides; most MHC class I molecules lack high-affinity peptides but traffic normally to the cell surface
- abnormal cytotoxic T cell physiology (MGI Ref ID J:64177)
- mice mount poor CTL responses to influenza virus, but normal responses to LCMV and vaccinia viruses
- decreased CD8-positive T cell number (MGI Ref ID J:64177)
- mice have few (15-20% of wild-type) mature CD8+ T cells in the periphery, but significantly more than Tap1-null animals
- hematopoietic system phenotype
- decreased CD8-positive T cell number (MGI Ref ID J:64177)
- mice have few (15-20% of wild-type) mature CD8+ T cells in the periphery, but significantly more than Tap1-null animals
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Tapbptm1Luc related
Hematological Research
Immunological Defects
Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Immunodeficiency (MHC class I deficiency)
Immunodeficiency (NK Cell Deficiency)
Immunodeficiency (T cell deficiency)
Research Tools
Immunology and Inflammation Research (MHC class I deficiency)
Virology Research
Reduced MHC Class I Responses to Specific Viruses
| Allele Symbol | Tapbptm1Luc | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Luc van Kaer | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Tpn-; | ||
| Mutation Made By | Andres Grandea III, Celltech | ||
| Strain of Origin | 129S6/SvEvTac | ||
| ES Cell Line Name | TL1/TL-1 | ||
| ES Cell Line Strain | 129S6/SvEvTac | ||
| Gene Symbol and Name | Tapbp, TAP binding protein | ||
| Chromosome | 17 | ||
| Gene Common Name(s) | D17Wsu91e; DNA segment, Chr 17, Wayne State University 91, expressed; NGS17; TAPA; TPN; TPSN; Tapasin; | ||
| Molecular Note | Insertion of a neomycin resistance cassette into the fourth exon. [MGI Ref ID J:64177] | ||
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Optimizing PCR Protocols
Grandea AG rd; Golovina TN; Hamilton SE; Sriram V; Spies T; Brutkiewicz RR; Harty JT; Eisenlohr LC; Van Kaer L. 2000. Impaired assembly yet normal trafficking of MHC class I molecules in Tapasin mutant mice Immunity 13(2):213-22. [PubMed: 10981964] [MGI Ref ID J:64177]
Tapbptm1Luc relatedChen M; Tabaczewski P; Truscott SM; Van Kaer L; Stroynowski I. 2005. Hepatocytes express abundant surface class I MHC and efficiently use transporter associated with antigen processing, tapasin, and low molecular weight polypeptide proteasome subunit components of antigen processing and presentation pathway. J Immunol 175(2):1047-55. [PubMed: 16002705] [MGI Ref ID J:100733]
Chun T; Grandea AG rd; Lybarger L; Forman J; Van Kaer L; Wang CR. 2001. Functional roles of TAP and tapasin in the assembly of M3-N-formylated peptide complexes. J Immunol 167(3):1507-14. [PubMed: 11466371] [MGI Ref ID J:120485]
Li L; Sullivan BA; Aldrich CJ; Soloski MJ; Forman J; Grandea AG rd; Jensen PE; Van Kaer L. 2004. Differential requirement for tapasin in the presentation of leader- and insulin-derived peptide antigens to Qa-1b-restricted CTLs. J Immunol 173(6):3707-15. [PubMed: 15356116] [MGI Ref ID J:92768]
Robbins SH; Tessmer MS; Van Kaer L; Brossay L. 2005. Direct effects of T-bet and MHC class I expression, but not STAT1, on peripheral NK cell maturation. Eur J Immunol 35(3):757-65. [PubMed: 15719366] [MGI Ref ID J:96620]
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]
Colony Maintenance
Breeding & Husbandry 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).
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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